Revealing mistake: When Shadow and Chance launch the cougar (mountain lion) off the cliff the cougar is completely still, basic instinct for all creatures would be to struggle, indicating the cougar was a fake.
Continuity mistake: Following Chance's run-in with the porcupine: Right after Animal Control pulled the needles out of his face/snout, he was visibly wounded, with giant red makings which appear on the right side of his face. Then, while the 3 pets are looking down at their hometown which they just realised is only a little distance from where they are (Sassy had just pointed this out to the dogs), those red wounds are now on the left side of Chance's face. Then, by the end of movie the same markings mysteriously disappear and are completely gone in the final scene.
Continuity mistake: Shadow is noticeably played by a different dog after he and the others arrive at the pound. The tell is the second dog has large black markings under his eyes, while the one seen earlier in the film does not.
Continuity mistake: At the mealtime in the kitchen, Sassy is appearing to be Siamese but seconds later she now looks like a Himalayan, which is her real breed in the movie.
Revealing mistake: Near the start of the journey, there is a shot of Chance and Shadow running through a creek. This is followed by a shot of Shadow coming toward the camera. As she turns off to the left screen, something on the bottom moves with her. It is likely a guide for the cat to follow.