Ash and his friends come across the Kanto Fair, and seeing a Charmander perform on stage reminds him of his old friend Charizard. He tells Iris, Cilan and N about his and Charizard's history, with Misty and Brock making cameos during the tale. Professor Oak sends Charizard over, and after he meets Iris' Dragonite, the two trainers agree to have a friendly match. Ash's offer to let Charizard rejoin his team is met with approval from all parties involved.

Ash and N prepare to save Iris, Cilan, and Professor Juniper's father from the clutches of Team Plasma before Ghetsis can revive Reshiram, but their attempts to fight back are hampered by Colress's Pokémon controlling machine, forcing them all to call back their Pokémon. Pikachu gets hit by the machine's beam, which sways N into surrendering the Light Stone in exchange for its freedom just as Ghetsis arrives, ready to begin the ritual.

After N is hurt by Colress's machine, two young women, Anthea and Concordia, come to save him. It is from these two girls that Ash and the others learn the truth about N's life, including his link to the evil Ghetsis.

As the revived Reshiram quickly falls under Ghetsis' control, Ash and friends try to develop a strategy to stop Team Plasma. Looker convinces Team Rocket to help in the fight against the villains, while Ash and Pikachu aim to destroy the controlling machine, and N hopes to pacify the enraged Reshiram before it destroys the world in a righteous fury - akin to when it burned down Team Plasma's castle in the past.

Colress appears and tests his newly-advanced machine on Dragon-type Pokémon - first taking over a young trainer's Haxorus, and later Iris's Dragonite. As Ash and Charizard try to stop them, N puts himself in the crossfire, knowing the Pokémon should be friends and not fight.

At the ruins dedicated to the Pokémon Reshiram, N steals the Light Stone from Cedric Juniper, and Ash's attempt to stop him ends with them separated from the others. Team Plasma move to attack the White Ruins while Team Rocket watch on in anticipation, and Iris, Cilan and Looker attempt to fight off the enemy forces.

The gang arrives in Opelucid City for Iris' scheduled rematch against the Dragon Master and Gym Leader Drayden, who handed her and Excadrill their first-ever defeat years ago. Upon arrival, Iris remembers her difficult time in going to school there and trying to adjust to urban life. She and the others then travel to the Opelucid Gym for her rematch with Drayden, where she puts her Excadrill and Dragonite to the test, respectively, against Drayden's Haxorus and Druddigon in order for him to evaluate her training and skills.

Team Plasma's Colress convinces Team Rocket's Jessie and James to use his technology on Meowth to make him stronger, but it is all part of Colress's plans to test his Pokémon controlling device.

The Unova League begins, and as the preliminary round matches get underway, Ash finds himself up against Trip.

Chili and Cress meet up with Cilan on Paladin Island as they have both been beaten by a challenger at the Striaton Gym named Morana who exclusively uses Ice-type Pokémon such as Mamoswine and Glalie. It is up to Cilan and Pansage to face off against Morana and her Abomasnow for the honor of the Striaton City Gym.

The group finally reaches the waters off of Kanto, just as Team Rocket once again tries to do their best to take Ash's Pikachu.

Near Vertress City, the gang meets the Pokémon Rescue Squad's Virgil - trainer of Team Eevee - and his brother Davey, whom they decide to assist in helping a group of troubled Cryoganal.

The third round of battles at the Unova League begins and Ash finds himself up against Stephan, putting Krookodile, Palpitoad, and Leavanny up against Stephan's Liepard, Zebstrika, and Sawk.

In the fourth round of matches, Ash battles against Cameron - who begins the match by revealing his secret weapon, Hydreigon.

While on Harvest Island, Ash and his friends meet the Pokémon Reporter Alexa, who has come all the way from the Kalos Region with her Gogoat and Helioptile. She has come to investigate Harvest Island's fruit harvest festival, which the others realize has a Pokémon Sumo tournament. Ash, Iris, and Cilan enter Pignite, Pansage, and Dragonite in the tournament to win the grand prize Focus Band.

With Iris and Cilan heading off on their own adventures in Johto, Ash is restless and still wishes to become a Pokémon Master. To that end, Alexa suggests that he travel with her back to her home in the Kalos region just as Team Rocket hatches another plan to steal Pikachu.

Ash and friends once again run into N, who has freed a Braviary held captive by Team Plasma. They help him bring it to a Pokémon Center, but when Braviary is tracked by a pair of Team Plasma Grunts - Nero and Bianco, who respectively use a Seviper and Zangoose in battle - N puts his life on the line. Successfully freeing Braviary, N joins the group on their journey to the White Ruins.

With Team Plasma defeated once and for all, Ash decides it is time to go back to Kanto. Iris and Cilan decide to go with him to further their skills, and Professor Juniper charters all of them a cruise through the Decolore Islands on a boat with a mysterious crew. Once settled in their cabins, however, Ash finds that they are locked in and their Pokémon are not with them.

Ash, Iris, and Cilan take a break on Capacia Island only to discover they have arrived on the one week once every 1000 years when Jirachi awakens and grants a wish. Gemma, a young girl who lives on the island, wants to ask Jirachi to bring prosperity back to the island, but Team Rocket has other plans.

On Cave Island, Ash and his friends meet up with Clair, Gym Leader of Johto's Blackthorn City, who has come to the island to capture a different-colored Druddigon, but her Dragonite left without her. When they find her Dragonite, Iris's Dragonite takes an instant dislike to it and the two fight, hampering Clair's plans to find the different-colored Druddigon on the other side of the island from the port.

On the way to Vertress City, Ash, Cilan, and Iris find their way to Iris's hometown: the Village of Dragons. While there, Iris shows Axew to her elder and helps her childhood friend Shannon when one of her Zweilous suddenly evolves into Hydreigon and goes out of control.

On the way to the Unova League, Ash and Cilan get challenged to a Tag Battle against the brothers Soren and Rocko who have trained their Braviary (Soldier of the skies) and Drilbur (Warrior of the land) to perform amazing combination attacks.

On a boat heading to see ruins dedicated to Reshiram, Ash, Iris, and Cilan meet the mysterious boy calling himself N, who quickly befriends their Pokémon. However, when Team Rocket attacks the group once more and James's Amoonguss paralyzes Pikachu with Stun Spore, N's timely intervention helps turn the tide of the fight.

Ash, Iris, and Cilan catch up with Professor Oak who has come to one of the Decolore Islands to investigate the Plasma Pokémon Rotom and its Forme Change capabilities. However, the Rotom native to the island are more interested in Pikachu, Emolga, and Stunfisk.

The appearance of Woodate Comet approaches, so Ash, Iris, Cilan, and Alexa go stake out the ruins where the legendary hero it is named after first spotted it. However, they must deal with several Ghost Pokémon and Team Rocket who are once again trying to capture Pikachu.