When Chance escapes from his kennel at San Francisco International Airport while leaving on a trip with the Seavers, his loyal friends Shadow and Sassy band together to follow him. And when the plane takes off with out them, the companions find themselves wandering the rough and tumble streets of the city by the bay, searching for a way back to where they live in the suburbs.

Refusing to let anything stand in the way of their reaching their destination, the pets are caught up in the most incredible adventure of their lives, and meet up with a whole new pack of pooches and mutts including Riley, Pete, Ashean, Spike, Stokey and Sledge, as well as the beautiful and seductive Delilah. Unavoidably confronted by danger, fun and excitement at every turn, Chance, Shadow and Sassy follow their hearts in order to return to the family who loves them.