As middle schooler Emily Elizabeth struggles to fit in at home and at school, her life takes a very sudden and unexpected turn when she meets a magical animal rescuer who gives her a small red puppy to look after. Little does she know that this teeny tiny puppy will very quickly grow (and grow) to become her best friend forever.
When Cli?ord becomes a gigantic red dog in her New York City apartment and attracts the attention of a genetics company who wish to supersize animals, Emily and her clueless Uncle Casey have to fight the forces of greed as they go on the run across New York City and take a bite out of the Big Apple.
Along the way, Clifford changes the lives of everyone around him, and teaches Emily and her uncle the true meaning of acceptance and love.