When aspiring medical student Lucas Ray (Jonah Hauer-King) finds a stray puppy, he immediately falls in love with her. He brings her home to the house where he lives with his mother (Ashley Judd). His mother also quickly falls in love with the puppy, whom Lucas names Bella (voice of Bryce Dallas Howard).

As she grows bigger, Bella and Lucas form the closest of bonds. But when his studies require more of his time, Bella longs for the days when Lucas was able to spend more time with her. She jumps out of a window in pursuit of a squirrel and while she's wandering in the forest, hikers spot her and assume she's a stray. They take her in, but Bella misses Lucas.

She sets off across 400 miles of dangerous Colorado wilderness to return home.

Based on the book of the same name by W. Bruce Cameron and adapted into a screenplay by Cameron and his wife, Cathryn Michon.