13-year-old Ichigo Momomiya is at an endangered animal exhibit with her crush Masaya Aoyama when she is hit by a beam of light and sees a cat entering her body. She begins to demonstrate cat-like behavior the following day. A giant monster attacks Masaya and forces Ichigo to transform into a pink magical girl with cat ears and a tail.

A boy named Ryou Shirogane explains that the monster she fought was a Chimera Anima—alien parasites that infect animals and turn them into giant monsters. Ryou and Keiichiro Akasaka, the owner of a pink cafe called Cafe Mew Mew, planned to take the DNA of five Red Data Animals and use them as biological weapons by injecting them into Chimera Anima—an experiment they called the Mew Project. But due to an earthquake the day before, the DNA was accidentally shot into Ichigo and four other girls that she met outside the museum instead!

Now a "biological weapon," Ichigo must fight against the aliens and find her potential teammates—all while keeping her feline identity a secret from Masaya.