Taking place in San Francisco, the series stars China Anne McClain, Sierra McCormick, and Jake Short as middle-schoolers in a gifted program at their local high school called the "Advanced Natural Talent" or "A.N.T." program. Zendaya guest starred in an episode portraying Sequoia Jones.
A.N.T. Farm revolves around Chyna Parks, an 11-year-old musical prodigy, who has just become the newest A.N.T. in the A.N.T. program at Webster High School. On her first day, she meets Olive Doyle, an odd girl who has a eidetic memory, and Fletcher Quimby, an artistic genius (but otherwise quite dim) who falls deeply in love with Chyna when they first meet. They soon become her best friends at the high school. They proceed to go on multiple adventures, using their talents to their advantage.
- China Anne McClain as Chyna Parks
- Sierra McCormick as Olive Doyle
- Jake Short as Fletcher Quimby
- Stefanie Scott as Lexi Reed
- Carlon Jeffery as Cameron Parks
- Aedin Mincks as Angus Chestnut