Kids from all over town converge to play Vanguard, a card game that seems to be the biggest thing going around. A timid boy, Aichi Sendō, has a rare card, the Blaster Blade, which makes him a target for Katsumi Morikawa, a player who wants to use Aichi's card to get revenge on another player, Toshiki Kai. After school, Morikawa and his buddy Yūta Izaki steal Aichi's Blaster Blade from him. Aichi runs to a card shop called Card Capital to find that Morikawa lost it in a bet against Kai. It is then that Aichi and Kai meet and play a round of Vanguard with Blaster Blade as the prize. Before the match, Kai gives Aichi Blaster Blade in the hopes of him using it effectively against him. During the course of the match, Kai teaches Aichi the rules of playing Vanguard. As the fight goes on, Aichi reveals that he has met Kai before when summoning his ace, Blaster Blade, which Kai gave to him long ago, stating that it was because of him that he wants to learn more about Vanguard.

After Aichi plays Blaster Blade, he and Kai recall their first meeting. Back then, after seeing a young Aichi beaten up, the young Kai cheered him up by giving him Blaster Blade, and he told Aichi to imagine himself as a strong warrior like the card. With that in mind, Aichi got absorbed into Vanguard, creating his own deck in the hopes of playing against Kai, who had already moved away by then. Back to the game, Aichi deals a bit of damage to Kai, who retaliates with his ace card, Dragonic Overlord. It wipes out Aichi's units and greatly damages him. All seems lost until Aichi draws a "Heal Trigger", which allows Aichi to stay in the game for one last turn. Aichi launches a final attack with Blaster Blade, which breaks through Kai's defenses and deals one more point of damage to Kai, thus giving Aichi the win. A day later, Aichi revisits the card shop. Despite thinking that Kai would not show up after being defeated, Aichi is glad to see that Kai returns.

Aichi's little sister, Emi, is worried by Aichi's different behavior as of late. After school, Emi sees Aichi with Morikawa and Izaki, who want him to go with them to the Card Capital. However, Emi misinterprets the situation as Aichi hanging with the wrong crowd. Concerned for her brother, she secretly follows the trio to the Card Capital. There, Emi is astounded by all the people in the shop, icluding Aichi, Morikawa, and Izaki, playing Vanguard. It is then that the card shop's manager, Shin Nitta, appears and introduces Emi to the world of trading card games. Emi and Shin then observe a cardfight between Aichi and Morikawa. The battle ends with Aichi winning without taking any damage. Watching Aichi play, Emi sees how much her big brother has changed because of Vanguard. And so, she has become supportive of Aichi playing the game.

After taking a look at Aichi's deck, Shin decides to show him "something nice". So, Shin has Aichi battle Misaki, who, despite working at the card shop, has never actually participated in a Vanguard fight before. Nonetheless, after Shin gives Misaki a special deck, she and Aichi begin their cardfight. In the midst of the battle, Misaki shows that she knows more about the game than she lets on as she draws multiple cards and calls her ace card, the Grade 3 CEO Amaterasu. Using the "Twin Drive" ability that Grade 3 cards have, Misaki defeats Aichi. Through this loss, Aichi learns that he has much more to know about Vanguard if he ever wants to play against Kai again.

Aichi goes to the card shop to buy a booster pack in the hopes of getting a Grade 3 card. When he arrives, he sees a grade-school kid, Kamui Katsuragi, convincingly defeating Izaki in a cardfight. Aichi challenges Kamui, but he refuses, noticing that Aichi is not a strong player. Then, after Kamui beats Morikawa in a cardfight, Aichi tries to buy a booster pack. Suddenly, Emi appears, and Kamui immediately falls in love with her. Before Aichi could buy a pack, Emi drags him back home while Kamui looks on, thinking that the two are boyfriend and girlfriend. Later, Aichi buys a booster pack and is pleased to find that the pack contained a Grade 3 card, Solitary Knight, Gancelot. Just then, Kamui shows up and challenges Aichi, demanding to get Emi if he beats him. Although Aichi misunderstands Kamui's intentions, he and Kamui begin their Vanguard fight. Kamui uses powerful cards like Genocide Jack and King of Swords to quickly deal a ton of damage to Aichi, who strikes back by using his newly-acquired Solitary Knight, Gancelot. But in the end, Aichi loses to Kamui after he calls his ace card Asura Kaiser. Afterwards, Emi arrives and tries to get Aichi home, and it is then that Kamui learns that the two are actually siblings. Now, hoping to get closer to Emi, Kamui starts referring to Aichi as his "big brother", although Aichi is not exactly glad about it.

Aichi and his friends decide to go to a different card shop called PSY. There, they try out the shop's special Vanguard Fight Stage. It oddly reacts to Aichi, which leads to a woman, Kourin, challenging him to a cardfight. When the two begin the battle, Aichi is surprised that the stage brings the cards to life. Aichi and Kourin, who both use a Royal Paladin deck, continue their battle, until Aichi makes a bad decision in not guarding one of her Vanguard's attacks, ultimately leading to his defeat. Afterwards, another woman, Suiko, gives Aichi the card The King of Knights, Alfred as a special memento for visiting the card shop. Later, Aichi learns from Morikawa that the card shop they visited has disappeared.

Shin introduces the "Standing Fight Table (Name Subject To Change)" to enrich the experience of a Vanguard fight, with Morikawa and Kamui being the first to play on it. After Kamui once again beats Morikawa, Aichi and his friends return to their homes but then see Kai walking back to his home. Wanting to learn where Kai lives, Aichi, Kamui, and Miwa try to follow him, but Kai soon notices them tailing him. Aichi apologizes and tries to get Kai to battle him again, but he declines. However, Kamui challenges Kai, and he reluctantly accepts. The next day, the two commence their cardfight. Kai gains the upper hand by getting a Grade 3 card, Embodiment of Victory, Aleph, into play before Kamui, who counterattacks with his own Grade 3 unit Mr. Invincible. But Kai soon summons another Grade 3 unit Vortex Dragon, and he later activates its Soul Blast skill to destroy some of Kamui's units, leaving Kamui unable to defend himself from Kai's final attacks. Kai defeats Kamui and takes his leave, but not before Aichi tells him that he'll become a stronger and more worthy opponent for him.

The Card Capital Shop Tournament begins soon, but Aichi is hesitant to play in it, even after making a new deck. However, when he learns that Kai will be in the tournament, Aichi decides to enter as well. But when he submits his entry application form, another Vanguard player, Osamu Kishida, places his application at nearly the same time as Aichi. Both of them want to enter, but there is only one open spot left in the tournament. To resolve this issue, Shin recommends to have Aichi and Osamu play against each other to see who gets the last entry spot. Using his Megacolony units' effects, Osamu restricts Aichi's units from standing while scoffing at him for calling so many weak units. However, Aichi uses his new card The King of Knights, Alfred, whose power is increased by the number of other Royal Paladins in play. With Alfred, Aichi defeats Osamu and is therefore officially in the tournament.

The Card Capital Shop Tournament finally begins. In the first round, Aichi must play against Izaki while at the same time, Morikawa battles Misaki. Since this is his first time in a tournament, Aichi grows nervous. His tournament jitters get the better of him as he makes many amateur mistakes. But when he sees that Izaki is also just as nervous and makes similar mistakes, Aichi realizes that he's not alone, regains his composure, and remembers that Vanguard fights should be fun. When he tells Izaki that, he too calms down, and the two continue playing the game at their best. In the end, not only does Aichi win, but Misaki also advances to the next round.

Kamui and Kai advance to the second round of the tournament, along with Ninja Master M, an eccentric player who dresses and acts like a ninja. He meets Aichi, who deduces that he is actually his teacher Mark Whiting, but he denies that claim (even though it's true). The tournament progresses to the second round matches with Aichi facing off against Ninja Master M while Kai plays against the previous tournament's champion Kazuki Inaba. Ninja Master M uses his Nubatama ninja units' effects to deplete the cards in Aichi's hands. He drives Aichi to a corner when he rides his ace card Stealth Dragon Voidmaster and leaves only one card in Aichi's hand. While this is going on, Kai defeats Inaba in his match.

Aichi makes a comeback by calling more units from his deck to boost the power of The King of Knights, Alfred, forcing Ninja Master M to use most of his cards to guard against his attacks. As a result, M is left with no cards to defend himself from Aichi's last attack. Aichi wins and therefore advances to the semifinals. Ninja Master M disappears, and Mark soon arrives (with a bag containing his Ninja Master M attire). After Aichi's match, Kamui and Misaki play in their respective cardfights, and they both advance as well. Before the start of the semifinals, the tournament is put on hold for a lunch break. So, Aichi and Emi have lunch outside the card shop where Kamui tries to get Emi to feed him, but no such luck. After everyone returns to the shop, Aichi, Misaki, Kamui, and Kai all draw lots to determine who will be playing against who. Aichi is put up against Kamui while Kai must fight Misaki. With the matchups set, the semifinals begin.

It's the semifinals: Kai plays against Misaki, and Aichi once again battles Kamui. Both Aichi and Kamui want to win for their own reasons; Aichi wants to fight Kai again while Kamui hopes to gain Emi's affection upon winning the entire tournament. Aichi defends himself from Kamui's Genocide Jack's attacks better than he did in their first cardfight. Aichi makes a surprising move by calling Blaster Blade as a rear-guard and using its ability to destroy Genocide Jack. As the battle between Aichi and Kamui rages on, the cardfight between Kai and Misaki comes to a close with Kai as the victor.

Aichi and Kamui's match comes down to the wire, with Kamui slowly building up his Vanguard's Soul. Despite Aichi getting a Heal Trigger to allow him to stay in the game, Kamui then uses his Mr. Invincible's Soulblast, dubbed the "Tornado Stand Galactica", making all of his units stand up and ready to attack again. With this move, Kamui once again defeats Aichi. After he gets over this loss, the final battle between Kai and Kamui ensues. Even though Kamui uses Mr. Invincible and its Soulblast like in the previous match, Kai nonetheless successfully defends and survives the onslaught. In the end, Kai beats Kamui again and is therefore the champion of the entire tournament. After the tournament, Shin then makes a special announcement: the four finalists (Kai, Kamui, Misaki, and Aichi) of this tournament are to represent Card Capital and participate in the regional tournament, shocking Aichi.

Kamui takes Aichi to Card Shop Handsome, a pirate-themed store that Kamui used to visit. They meet the national-tournament-level and previous regional champions Team Handsome, which is led by Gouki Daimonji. Soon after, they also meet Gouki's little sister Nagisa. She has a huge crush on Kamui to the point that she wants to marry him despite their young age, but he does not feel the same way about her. When Kamui tries to explain that he's in love with Aichi's sister Emi, the situation is misinterpreted as Aichi trying to take away Kamui and hurting Nagisa's feelings. Wanting to make her little sister happy, Gouki challenges Aichi to a Cardfight with the winner getting Kamui. As the fight goes on, Aichi learns the horror of Gouki's Granblue deck as he constantly resurrects his undead pirates from the Drop Zone. The level of a Cardfighter who has played in a national tournament proves to be too much for Aichi; Gouki beats Aichi, learning the level of competition that he will face in the future. After the game, the misunderstanding is cleared, and Nagisa goes back to chasing after Kamui, much to his dismay.

As Emi continues coming to the Card Capital Card Shop, Shin convinces her to try the game out for herself. While approaching the game shop, Katsumi has his fortune told and he finds that he will have luck with his juniors today (however, Yuta corrects him and says that he'll have terrible luck today). When they arrive at the card shop, Aichi is surprised when Emi is preparing to play Vanguard. Emi is handed Misaki's deck as Shin wants both Aichi and Emi to battle together. However, Katsumi wishes to take Aichi's place and a battle between the new player Emi and the "Expert Naive Player" Katsumi begins, with Kamui bitter about how Katsumi is playing against her instead of himself. Despite only using "cute" cards, Emi defeats Katsumi with some beginner's luck.

The day for the regional tournament is here. Shin drives the team of Aichi, Kamui, and Kai to the tournament site. on the way there, while Aichi and Kamui make adjustments to Aichi's deck, Shin decides to name the team "Quadrifoglio" (Italian for "four-leaf-clover"; Q4 for short). They arrive and watch a promotional video of the pop idol group Ultra Rare, who are the three girls, Kourin, Rekka, and Suiko, who Aichi met at the card shop PSY. After a run-in with Team Handsome, it is then accounced that Team Q4 will play in the first round against Team Black Magic, three dark-robed men who all have "Kuro" (Japanese for "black") in their names. Because of Misaki's absence, Aichi will have to participate, and in the first match, too! Aichi's fight does not go well. His opponent, Kurosawa, appears to use the same clan as Kai, the Kagero, but with many new units. When he Superior Rides Demonic Dragon Berserker, Yaksha and uses several skills to retire all of Aichi's Rear-Guards, Aichi panics, realizing that even if he rides Alfred, he cannot use fully use its ability. In a desperate move, he uses all the cards in his hand, including the newly-added Knight of Truth, Gordon, to create an almost full field.

Aichi has difficulty pushing for victory, and his opponent gets a Critical Trigger on top, bringing him to five damage. Aichi desperately needs to block the next strike, but is unwilling to leave his hand empty. He guards with Wingal and Intercepts with his new unit Knight of Truth, Gordon. At first, it seems that Aichi has an insufficient amount of Shield, but he reveals that Gordon's skill, the Especial Intercept, allows its shield to rise by 5000 points during an Intercept. Aichi then proceeds to call Gigantech Charger, another new card whose skill is used to completely fill Aichi's side of the field, and finish the match with a Critical Trigger. Team Black Magic's next fighter, Kurosaki, appears, while on Team Q4's side, Kai steps up. They both use Kagero, and the announcer, MC Miya, and spectators seem to think it will be an exciting match. However, they are soon disillusioned - Kai annihilates his opponent without even breaking a sweat. Afterwards, everyone sees that underneath Team Black Magic's dark cloaks are actually three sparkling-bright young men. Kai's victory leads to Team Q4 advancing to the next round and Kamui becoming enraged that he was not given the chance to fight.

The regional tournament continues with Team Q4 easily plowing through their second and third opponents, Team Martial Arts and Team Chemistry Club, by defeating them both 2-0. Kamui's past relation to Gouki and Team Handsome is revealed, and Gouki and Kamui pledge to be the first to take the stage in the final match. During a break, Emi arrives with lunch, making Kamui happy to eat her food. But this moment is ruined when Nagisa charges in with her own prepared lunch and messes things up for Kamui. Incidentally, both lunches end up in Morikawa's stomach, who spews fire like a dragon from the spicyness of Nagisa's food, which Kamui does not appreciate. After a musical performance by Ultra Rare singing their opening hit song "Miracle Trigger", the tournament finals commence. Kamui, expecting to play against Gouki in the first game, is shocked when Nagisa steps up to be his opponent.

Surprisingly enough, Nagisa steps into the fray as the first fighter of Team Handsome, resulting in Kamui being in a desperate situation as she declares that Kamui has to marry her if she wins. Kamui answers back by declaring that if he wins, then Nagisa will leave him alone. Both parties agree to these terms and then start their Cardfight. Using a Nova Grappler deck like Kamui, Nagisa proves herself to be an excellent fighter, fighting toe-to-toe with him. Though it seems that the agonizing Kamui can make a reversal using Lion Heat, Nagisa is able to fully negate his attacks and finish him off using her own Lion Heat and Magician Girl, Kirara with a "Wedding Hold" during the next turn. After the match, as per agreement, Nagisa gets dressed in a wedding gown and is ready to marry Kamui, who tries to run for his life.

In spite of Nagisa winning and her getting to marry Kamui as a result, Kamui weasels out by saying that Team Q4 as a whole hasn't lost yet, so their agreement is still pending. With one loss in their record, Team Q4 has to win both the next matches in order to advance through the regional tournament. Though everyone is certain that Kai will win, Aichi becomes increasingly desperate, as his match will be the one to decide the fate of the team, going as far as to thinking of running away to have Misaki participate instead. As Kai walks up to play, he indirectly tells Aichi that people who run away are not worthy of fighting him. His opponent, Kaoru "Ka-boom!" Komatsubara, seems to be a formidable opponent who gloats how he's a national-tournament-level player, but Kai gains an early lead, pushing his enemy into a bad situation. Throughout the battle, Kai chooses to not defend against all except one of Kaoru's attacks, puzzling everyone about his decisions. Aichi believes that Kai is trying to tell him something through these actions; he deduces that Kai knows that he does not need to defend and will still be able to win. When both players are at five damage, Kaoru confidently declares that he will survive and claim victory, but Kai refutes that claim, loudly announcing Final Turn! He rides a new card, Blazing Flare Dragon, and uses a card skill to retire one opposing unit and increase its attack power. Kai relentlessly adds to the power by drawing two Critical Triggers in a row, thoroughly annihilating Kaoru. Seeing Kai's power, and remembering his own aspirations to reach his level, Aichi becomes motivated to win his fight!

Aichi's match against Gouki begins. Aichi remembers Gouki as a formidable opponent, and realizes that he cannot stay the same as before if he wishes to win. Using a combination of the skills of Barcgal and Knight of the Future Llew, he Rides Blaster Blade from the deck, surprising Gouki. With both sides getting a Heal Trigger and staying at nearly the same amount of damage, it becomes an intense fight. Gouki Superior Rides Spirit Exceed from the Drop Zone and prepares for a full frontal assault.

The fight between Aichi and Gouki continues. Aichi blocks Gouki's attack, and counterattacks with Alfred, bringing Gouki to five damage. However, Gouki replaces his Vanguard with King of the Demonic Seas, Basskirk, who uses eight cards from the Soul and five cards from the Damage Zone, to instantly revive as many Granblue units from the Drop Zone as possible! Though Aichi perfectly defends during that turn, he realizes that he must finish it immediately. A strange blue light emerges from his deck, which Kai notices. Aichi draws into one of the new cards that he had acquired, which he had put in his deck despite Kamui's advice. He rides Soul Saver Dragon, the powerful God of the Royal Paladin knights, and activates its skill to power up his rear-guard units. Though it seems like Gouki will make it past, Aichi Drive Checks a Stand Trigger, and finishes the game with a brutal attack. With Aichi's win over Gouki, Team Q4 wins the regional tournament and is therefore eligible to enter the national tournament. At the awards ceremony, Ultra Rare congratulates Q4 for their victory, and Suiko invites Aichi to visit PSY once more.

Aichi, Kamui and Misaki visit Card Shop PSY after Suiko's invitation. They meet an aloof red-haired stranger with a peculiar attitude. However, once the Ultra Rare group arrives, they learn that he is none other than Ren Suzugamori, the winner of the previous national tournament! Kourin and Ren engage in a Cardfight, both using the exact same deck structure, and Aichi, who had been beaten by Kourin before, watches in amazement as Ren easily controls the match. Strangely using the same speech patterns that Kai does during his matches, Ren uses a seemingly simple Grade 1 card called Blazer Idols to finish the game. However, what are these visions that Aichi has of the planet Cray, when Ren is about to make his move...?

To prepare for the national tournaments, worried about Cardfighters on Ren's level, Aichi and Misaki engage in a fight. However, memories of her tragic past surface in Misaki's mind, causing her to break down. Though she dominates the match by preventing Aichi's strategy from taking effect until it is too late, and finishing him off by means of a Critical Trigger, she abandons the team directly afterwards, claiming to be unable to fight any longer. Stunned, Aichi and Kamui try to discover what they have done wrong...

Emi visits Card Capital, worrying about the depressed Aichi. She encounters Misaki, who claims not to know anything - but the manager pushes the two into a cardfight using the new trial decks that just arrived. Going along for Emi's sake, Misaki uses the new Nova Grappler deck, whereas Emi uses the Oracle Think Tank one. Already having memorized all effects of the cards with her perfect memory, Misaki easily defeats Emi, but in doing so, she remembers the fun that Vanguard used to be for both her and her parents, and realizes that they would not want her to feel sad about the game. Receiving a key from her uncle to unlock the box with the deck her parents made for her, she rejoins Team Q4 to Aichi and Kamui's joy, who feel terrible about what had happened, and easily beats every regular customer of the shop.