In Tokyo, Japan, a young girl named Ichigo Momomiya attends an endangered species exhibit with her "crush" Masaya Aoyama. After an earthquake, Ichigo and four other girls are bathed in a strange light. A cat appears before Ichigo, then merges with her. The next day, she begins acting like a cat and making cat puns. After meeting Ryô Shirogane and Keiichirô Akasaka, Ichigo learns that she was infused with the DNA of the Iriomote cat. Ryou and Keiichirou explain that this allows her to transform into Mew Ichigo, a powerful heroic cat girl. She is ordered to defeat Chimera Animas—alien parasites which infect animals and turn them into monsters. Ryou and Keiichirou instruct Ichigo to find the four other girls from the exhibit—the remaining Mew Mews.
The first Mew Mew Ichigo encounters is Minto Aizawa, a spoiled, wealthy girl and ballerina who is infused with the genes of the blue lorikeet;[n 1] Retasu Midorikawa, a shy but smart girl who endures constant bullying from three girls and absorbs the genes of the finless porpoise; a hyper and yet young girl named Bu-Ling Huang who receives the genes of the golden lion tamarin; and Zakuro Fujiwara, a professional actress and model infused with the genes of the gray wolf.
The five Mew Mews battle the Chimera Animas and their alien controllers Quiche, Pie and Tart. Quiche falls in love with Ichigo where he tries to gain her love despite the fact that he is trying to eliminate the other Mew Mews.One of the Mew Mew gets attacked and dies from an alien bite, but then comes back to life. Pie and Tart later join Quiche in trying to destroy the Mew Mews.