Ortaokul öğrencisi Emily Elizabeth, kendisine küçük ve kırmızı bir köpek yavrusu hediye eden büyülü bir hayvan kurtarıcısı ile tanıştığında, New York City'deki küçük dairesinde on metrelik dev bir köpek ile karşılaşabileceğini hiç tahmin etmemişti. Bekar annesi iş için uzaktayken, Emily ve eğlenceli ama çoğu zaman içinden geldiği gibi davranabilen amcası Casey, heyecan dolu bir maceraya atılacak.

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.

Fearing that he costs too much to feed, Clifford decides to join a traveling carnival so he can enter a talent contest in hopes of winning a lifetime supply of Tummy Yummies treats. Joined by his friends Cleo and T-Bone, Clifford meets up with Shackleford the High-Flying Ferret and Rodrigo Chihuahua of Steel, as they work together to turn a broken-down act into a record-breaking show.