While Ichigo Momomiya was at an endangered speciesMasaya Aoyama, an earthquake strikes. Ichigo, and four girls she just met, are bathed in a strange light. Ichigo sees an cat floating in front of her that merges with her. The next day, she finds herself acting like a cat. After meeting Ryou Shirogane and Keiichiro Akasaka, she learns that she was infused with the DNA of the Iriomote wildcat so that she can transform Mew Ichigo, gaining special powers and a new appearance, so that she can defeat the Chimera Animas, alien parasites that infect animals and turn them into monsters. Operating out of the Cafe Mew Mew, Ryou and Keiichiro tell Ichigo to find the other four Mew Mews to help in the battle: the other four girls who were at the exhibit. exhibit with her crush and future boyfriend,The first Ichigo finds is Mint Aizawa, a spoiled, wealthy girl infused with the genes of the Ultramarine Lorikeet. The second is Lettuce Midorikawa, who was being picked on at the museum and who is infused with the genes of the finless porpoise. Lettuce is at first terrified of what has happened to her and confused about her new powers, and attacks the other two Mew Mews. Ichigo and Mint are able to calm her down and help her realize that rather than losing friends, her new powers have helped her gain some. Young Pudding Fong, infused with the genes of the golden lion tamarin, is the third found. The final Mew Mew, model Zakuro Fujiwara, is infused with the genes of the gray wolf and at first refuses to join the others but changes her mind after they come to help with Kish targets her.
With the five Mew Mews gathered, they find themselves not only having to battle the Chimera Animas, but the three aliens who are setting them lose on the Earth. Desiring to remove all of the humans from the world in preparation for the awakening of their leader Deep Blue, the aliens lived on earth long before the humans and now wish to reclaim it. Kish, the first to show himself, falls in love with Ichigo, but doesn't let that stop him from trying to get rid of the other Mew Mews. He is joined by Tart, who particularly hates Ichigo, and Pie, who is calmly analytical in his attacks on the Mew Mews.
Ichigo learns that they have a limited time to stop the aliens as the cat DNA inside her is trying to become more dominate, causing her to change into a cat when excited. As the fighting gets more intense, the Mew Mews begin to hunt for "mew aqua" which is created from pure, clean water and that contains the power to undo some of the alien's worse attacks. They are also joined by the mysterious Blue Knight, who says he was born to protect Ichigo. When Kish kidnaps Ichigo while she's on a date with Masaya, they learn that Masaya is the Blue Knight, a mysterious man who had been aiding the Mew Mews and protecting Ichigo. His desire to protect Ichigo, whom he loves, manifested itself in the form of the Blue Knight.
However, just as the Mew Mews and the Blue Knight think they are starting to win the battle, Masaya collapses and transforms again, this time into Deep Blue, the alien leader who wants to destroy all of humanity. Explaining Masaya was just a false form he created to house him while he slept, Deep Blue attacks Ichigo and the others. Masaya is able to retain enough of himself to use a nearby mew aqua drop to destroy Deep Blue, killing himself in the process. Crying over his body, Ichigo pours all of her power into him to save his life, but doing so causes her to briefly die instead. He kisses her, which causes her to change back to normal and revives her. After saying their goodbyes, the Kish, Pie, and Tart return to their own world.
