As Emily struggles to fit in at home and at school, she discovers a small red puppy who is destined to become her best friend. When Clifford magically undergoes one heck of a growth spurt, becomes a gigantic dog and attracts the attention of a genetics company, Emily and her Uncle Casey have to fight the forces of greed as they go on the run across New York City. Along the way, Clifford affects the lives of everyone around him and teaches Emily and her uncle the true meaning of acceptance and unconditional love.

Lester and Orville accidentally launch a rocket which is supposed to fly to Mars. Instead it goes to New Orleans for Mardi Gras. They are then forced by bank robber Mugsy and his pal Harry to fly to Venus where they find a civilization made up entirely of women, men having been banished.

Comença l'espectacle amb la primera gran aventura de Clifford, el gran gosset vermell i els seus inseparables companys Cleo i T-Bone. Els nostres amics decideixen presentar-se al popular concurs Tummy Yummies en què es busquen les mascotes amb més talent del país. Però Clifford, Cleo i T-Bone no hi seran sols; els acompanyen un grup d'hàbils mascotes com Rodrigo, el chihuahua; Dirk, el gos salsitxa; Dorothy, la vaca acròbata i Sakelfor, la fura voladora, amb qui viuran una infinitat d'aventures.