The school rhythmic gymnastics team sees Ichigo avoid the path of an on-coming bus by leaping over it, and the team recruits her. A promise from Masaya to come and cheer for her at the competition changes Ichigo's participation from reluctant to enthusiastic. After Ichigo's spectacular individual performance, Kish attacks with a chimera anima. After the Mew Mews defeat the monster, competition continues; but Ichigo's performance drops during her team's round due to exhaustion from the fight. The team is happy with their second place win and names Ichigo the team's Most Valuable Player.

Ichigo meets a shy and timid girl named Lettuce Midorikawa. Later at the café, Ichigo sees her with three other girls, who are trying to coerce an unwilling Lettuce to try to photograph a rumored school ghost. Ichigo "accidentally" dumps parfaits on them to get them to leave Lettuce alone. After work, Mint and Ichigo go to the school to investigate the "ghost". Instead, they find Lettuce who was afraid of being isolated because of her new powers and started "haunting" the pool. After a brief fight, Ichigo and Mint calm her by explaining her Mew powers and welcome her to the team. While Ichigo is walking home, an alien named Kish appears, steals her first kiss, and introduces himself before disappearing again.

The girls win a day-trip to a resort in the mountains. On the way up the mountain, they stop at a shrine to eat lunch where a boy named Masazou Aoyamada yells at them for desecrating the shrine of Bacchigappa, the god of the mountain. The girls find a natural hot spring and stop to relax. There they learn that the resort is under construction and that their prize trip is for the following year. Masazou tries to stop the construction workers, claiming that the work has scared away the local otters and is destroying their habitat. Kish arrives and steals the boy's spirit to create a chimera anima. The Mew Mews defeat the monster and restore Masazou's spirit. The incident prompts the other villagers to join in Masazou's cause to oppose the construction.

While at Mint's house to borrow a dress, Ichigo meets her older brother, Seiji, who is going to study abroad. She is saddened to learn that they have grown apart after seeing an old photo of the two. Wanting to help the siblings reconcile, Ichigo invites him to attend Mint's next ballet performance. When the girls bring Seiji to Mint's dressing room before the performance, Mint maintains her distance from her brother. As he is leaving, a chimera anima attacks and Seiji tries to protect Mint. After the Mew Mews defeat it, Mint again tells Seiji he should not waste his time there. He gives her a bouquet of flowers and tells her that she is still important to him.

One night, a mysterious girl saves two people from a chimera anima. At the café, the girls read a newspaper article about the incident and realize that none of them is the girl shown in the picture. Mint arrives and recognizes the girl as Zakuro Fujiwara, a famous model whom she idolizes. Ryou sends the girls to an audition to meet her, but Pudding's tricks nearly get them kicked out. That night, the girls find her praying at a church where she is attacked by a flock of crows infected by chimera animas. Before the girls acted, Zakuro transforms and defeats them all. Afterwards, the girls are shocked with she refuses to join them and dismisses them as annoying.

Mint is upset by Zakuro's rejection, and the others try to cheer her up. Ichigo and the others go to talk to Zakuro. Meanwhile, Kish approaches Zakuro and offers her a deal to return her body to normal if she joins him. When the girls arrive, Kish traps Mint, Lettuce, and Pudding in an alternate dimension. He then demands a fight between Ichigo and Zakuro in exchange for the trapped friends. Ichigo refuses and returns to the café where Ryou encourages her to trust in Zakuro and share her feelings. While shooting a television show, Zakuro is attacked by a chimera anima. Ichigo arrives and battles the monster while Zakuro saves the others. After its defeat, Zakuro agrees to be a part of the team. Apparently, the entire battle was aired on live television, and so they introduce themselves to Tokyo as the protectors of justice, "Tokyo Mew Mew".

Keiichiro begins making a beautiful birthday cake for someone, and the girls ponder whom it might be for. Later, Ichigo meets a woman named Rei studying butterflies. She later learns that Rei is Keiichiro's ex-girlfriend, and the intended recipient of the cake. Even though they separated due to their different interests and jobs, he continues making her new birthday cakes for her. The girls try to get them meet again to resolve their lingering feelings. At Rei's house, her spirit is stolen by Pie and Tart and used to make a chimera anima. With help from Keiichiro, they are able to defeat the monster and retrieve Rei's spirit. In the end, Rei and Keiichiro truly go their separate ways.

Mint surprises the other girls by inviting them to a tea party. When they arrive, they meet a spoiled, wealthy girl named Kanna, who declares that she is Mint's "eternal rival." A box arrives, containing something Mint wanted to share with everyone. Watching nearby, Kish believes it must be mew aqua and tries to take the box. Not realizing the danger, Kanna takes the box back. Kish unleashes a chimera anima and Mint rescues the girl from the monster. The others transform and fight the monster, but are losing until the Blue Knight arrives and reveals its weak point allowing Mew Ichigo and Mew Mint to defeat the monster. Afterwards, Kanna admits she has always envied Mint. The box is opened to reveal that it is a special tea that Mint wanted to share with her friends. They invite Kanna to join them, but she declines and promises to invite them to her house for even better tea.

The aliens decide to use special chimera animas to release pollutants into Tokyo Bay. The Mew Mews arrive, sans Lettuce, and find themselves having to fight numerous smaller chimera animas made from fish. Mew Lettuce and Ryou arrive by boat, but the larger monster destroys it and they are thrown into the water. While the others defeat the fish monsters by combining Mint and Pudding's attacks, Lettuce tries to save the drowning Ryou. Her emotions activate the mew aqua around his neck, causing her legs change to a porpoise fin and easily bring Ryou back to the surface. The mew aqua weakens the remaining chimera anima, enabling them to defeat it.

Ryou and Keiichiro tell the girls to take a vacation, feeling the final battle is approaching and wanting them to be refreshed. Ichigo, however, cannot find Masaya to enjoy the downtime with. Meanwhile, Kish tells Pie and Tart that he is going to use the Blue Knight's powers rather than waiting for Deep Blue to awaken. Pie disagrees, but Tart is convinced. They release all the chimera animas they have in order to distract the Mew Mews and the Blue Knight, while the aliens search for Masaya. Ryou realizes it is a trap and sends the Mew Mews to find Masaya as well. When the girls eventually find him, he is lying unconscious. Mew Ichigo approaches him, but he transforms into the Blue Knight. All of the strange energy in the city gathers around him and he transforms again, into Deep Blue.

Returning from the grocery store, Ichigo stops to rest on a bench. A young girl, Pudding Fong, begins performing acrobatic tricks in front of her and then demands a tip. Ichigo gives her a piece of candy then runs off. Angered, Pudding causes Ichigo's cat ears and tail to pop out. Amazed, Pudding chases Ichigo wanting her own set of ears and tail in order to make money. Ichigo finally yells at her but later at the café feels sorry for the girl as they wonder why she wants to make money so badly and goes to apologize. The next day, Kish attempts to steal Pudding's spirit, but the Mew Mews stop him. Using the spirit of another human stolen earlier, he attacks with a chimera anima. While protecting Ichigo and Mint, the monster's attacks; Pudding's mew mark is revealed and she transforms into Mew Pudding. She quickly helps them defeat the monster and is ecstatic to join the Mew Mews.

Masaya takes Ichigo to Inohara Park to show her a large cherry tree that is unusually blooming out of season. The next day, Keiichiro discovers that five cherry trees have been infected by the aliens explaining the early blooming. The Mew Mews set out to destroy them simultaneously, or the trees will release a poison dangerous to Tokyo. Mew Ichigo takes the tree in Inohara Park, where Kish waits for her. A fight keeps Ichigo from attacking the tree, and it begins releasing its poison. Ichigo jumps into the tree and successfully destroys it. After Kish leaves, Mew Ichigo finds Masaya standing behind her after he called out "Ichigo".

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While cleaning the café, a woman approaches Ichigo and Lettuce and begins speaking to them in English (Spanish in the 4Kids dub), but they cannot understand her. Masaya appears and translates for them. The woman, Mary McGuire (Maria Rivera in the 4Kids Dub), is a pianist who Ryou asked for a performance at an upcoming formal party to reward the girls for their good work. During the party, Kish appears and uses a new technique to steal Mary's (Maria's) spirit to create a chimera anima. During the battle, he mentions the name of the mysterious alien leader, Deep Blue. The girls use Mary's (Maria's) music to weaken the monster, enabling the girls to defeat it and return her spirit back to her body.

Worried Masaya discovered her identity, Ichigo avoids him. Later, Ichigo intends to cheer for Masaya during a kendo match but is unable to face him. Later, a jealous Kish attacks him with a chimera anima capable of recreating itself when attacked. Ichigo tries to fight the monster but is unable to destroy it. Kish tells her that he will let Masaya go if Ichigo becomes his, but Ichigo refuses and instead dives into the slime and grabs Masaya's hand. Her body begins to glow and she breaks free, destroying the monster. Kish retreats and Masaya apologizes to Mew Ichigo for calling her "Ichigo", explaining that she looked like someone he knew. Later, he thanks Ichigo for coming to cheer for him and ties a bell collar around her neck so she cannot run from him anymore. Disappointed in Kish's continued failures, Deep Blue sends two more aliens, Pie and Tart, to help him destroy the Mew Mews.

Mint has a strange dream in which she is talking with her merged animal, the ultramarine lorikeet. Later at the café, Ryou and Keiichiro tell the girls about a substance called mew aqua and its power. After her dream, Mint is concerned about their mission. When she learns the late-arriving Ichigo was on a date with Masaya, she gets angry and stomps out of the café. Later the girls receive a package with Mint's pendant and uniform in it. Zakuro goes to talk to her while the others begin searching for mew aqua. The aliens are also searching for it and find it just as Ichigo, Lettuce, and Pudding appear. Kish merges five parasites into the mew aqua, creating a powerful new chimera anima. The girls are struggling to fight it but Mew Zakuro is able to convince Mint to transform and together they defeat the monster. They learn the mew aqua was a fake and Mint apologizes to Ichigo for her earlier actions.

Ichigo meets a cat at the train station and discovers that, even in her human form, she can understand him. The cat, named Asano, later comes to the café, and tells her that he is searching for the cat he loves, a Lilac Point Siamese named Jacqueline whose owner moved away. The girls agree to help him find her, but learn that her owner has taken her to a cat fair to find her a fiancé. Asano speaks to her there, but she says she cannot leave her owner because she is his most precious memory of his late wife. When one of the other cats is turned into a chimera anima, Asano comes to Jacqueline's aid. After the girls defeat the monster, Jacqueline's owner decides to allow the two cats to be together.

When Ichigo's father finds out that she has a boyfriend, he does not approve. He demands that Masaya defeat him in a kendo match before he will allow them to continue dating. Ichigo complains to her mother, who explains that her father loves her and just wants to protect her. Her mother also tells her that they too had to fight to be together when they were young. Ichigo rushes to stop the fight, reminding her father of the past and how her mother did the same thing for him. Though he does not want to face that his "little girl" is growing up, he grudgingly gives his approval of the relationship.

The girls participate in an open market where Lettuce sells a variety of dolls that she made herself, which are popular with the crowd. The last doll is purchased by famous doll maker Ayano Uemura who invites Lettuce to work with her at her workshop. Lettuce happily accepts and they make a doll together that Ayano takes to an exhibition. When the girls go to see the doll, they discover that Ayano took all of the credit for making it and denies that Lettuce helped her. Kish appears and steals Ayano's spirit to make a chimera anima. The girls transform and defeat the monster, returning Ayano to normal. Afterwards, Ayano confesses that she was envious of Lettuce's talent and had run out of new ideas. Lettuce forgives her, and tells her she does not care whose name is on the doll as long as it makes people happy.

Ichigo tries to talk to Ryou about the problems caused by her cat genes, but he ignores her. On the way to school, Ichigo changes into a cat again and gets in trouble, but is saved by Alto who also kisses her to change her back to normal. Despite his struggling, Ichigo picks him up and is shocked when he suddenly changes into Ryou. After school, she goes to the café where Keiichiro tells her the history of the Mew Project, which was started by Ryou's father. After his parents were killed by an ancient chimera anima, Ryou decided to continue his father's research. Wanting to be sure the merging process was safe, he tested it by merging himself with cat genes. This gave him the ability to change into a cat at will, but only for 10 minutes at a time or he will remain a cat permanently. Ichigo promises to do her best as a Mew Mew.

As Christmas approaches, Ichigo grows depressed as she thinks about how she is regularly lying to Masaya to hide her being a Mew Mew. Zakuro invites her to go shopping with her and tells Ichigo that since she cannot open her heart, she should give Masaya something that reflects her feelings. Ichigo chooses a necklace called "Tears for Christmas." She is still initially reluctant to face him, but finally arranges to meet him at the big Christmas tree in Odaiba. While she is waiting, the aliens attack. When Ichigo transforms, her emotions cause mew aqua to materialize at the top of the tree. Joined by the others, the Mew Mews prepare to fight the aliens to acquire it.

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The group is searching for mew aqua around a large rock formation in the forest when the girls and Masaya get separated. Something strange begins happening and everyone transforms. Masaya transforms into the Blue Knight, but falls from the rock and returns to normal. Kish confronts him and reveals that he cannot maintain his Blue Knight form if he is not protecting Ichigo. The alien moves to kill Masaya, but Mew Ichigo transports and appears between them. Masaya is knocked unconscious as Kish tries to kill Ichigo. This triggers Masaya's transformation, but his powers go out of control due to his rage at Kish. The other Mew Mews teleport to Mew Ichigo just in time to put up a shield around her as the rock explodes from the Blue Knight's power. Masaya returns to normal, seemingly unharmed. Kish tells Pie and Tart that the Blue Knight is the one who can save them.

The girls wonder about Masha's usefulness beyond just detecting chimera animas and eating the parasites. The discussion leads Masha to question his confidence. While the Mew Mews fight a chimera anima, he tries to fight alongside and ends up swallowed by the monster. Tart and Pie retreat to the alien dimension. Upon discovery of Masha, Pie tries to extract Masha's data. In turn, Masha uses the connection to the aliens' computers to send a message to the girls, enabling them to find a way to the dimension. Before they leave, Ryou gives Ichigo a new weapon, the Mewberry Rod. When the girls reach the alien area, they are quickly captured, but Masha gets himself free and rescues them. Ichigo uses her new attack to destroy the chimera anima, allowing them to return to their own dimension. Masha promises not to try to fight anymore.

The data gathered by Masha reveals that the aliens originally inhabited the earth, but had to leave because of changes in the environment, ending up on an even worse planet. Ichigo is upset at this, but Ryou reminds her that it is not an excuse for trying to kill humans. Ichigo goes on a date with Masaya, which cheers her up, but the next day she is sick with a cold. The girls and Masaya visit, but after he leaves Kish appears. Ichigo escapes out a window, while the others prepare to battle multiple chimera animas released by Pie and Tart. Too weak to fight, Ichigo is unable to protect herself from Kish, but is suddenly rescued by a mysterious alien who introduces himself as The Blue Knight.