When Emily Elizabeth (Darby Camp) finds a small red colored dog named Clifford, she brings him home to her Uncle Casey’s (Jack Whitehall) place, asking him to take care of Clifford for just one night. To their surprise, Emily and Casey find Clifford to have grown up to 10-feet-tall the next morning. Intimidated by his sheer size at first, Emily and her uncle start to develop a strong bond with Clifford, along with their friends and neighbors. However, a genetics company catches wind of Clifford, and want to take him to their lab for experimentation. Now running from greedy scientists, Emily, Casey and their friends must come together to protect the big red dog they have all grown to love.