The show tells the story of Anne Boonchuy, a self-centered 13-year-old who is magically transported to the fictitious world of Amphibia, a rural marshland full of frog-people. With the help of an excitable young frog named Sprig Plantar, Anne will transform into a hero and discover the first true friendship of her life.
Amphibia is one of the few non-action cartoons to have a human character animated with five fingers. The anthropomorphic amphibians having four fingers makes sense since real-life amphibians have four digits on their hands.
The episode title cards depict a wood carving in darkness lit up with the title superimposed over it. This is an actual wood carving that is photographed and reused every episode.