Bob takes Lassie and Neeka, an Alaskan native, to see the cliff dwellings at Mesa Verde Park. While exploring Neeka falls, breaking his leg with Lassie going for help. A daring and dangerous rescue is conducted by the rangers.
Clint and Edie, along with Clint's guide dog Ginger, live in a remote area of the forest. Bob leaves Lassie for a visit so when Edie is injured Lassie leads Clint to her. Lassie goes for help while Ginger faces a mountain lion.
Lassie finds happiness with Sgt. Hayes learning to herd sheep on his ranch. She has three pups with his collie Duke but the sergeant is under the mistaken belief a killer wild dog is the father. Lassie runs away to save her puppies.
After Lassie leaves the Hayes Ranch she finds shelter in a small cave with her pups but has no food or water. A young mute boy Kerry finds them, bringing them food but learns he is to be sent away to school. He then runs away.
The Holts and their friends search for the runaway Kerry but he is with Lassie and her pups. After a dangerous encounter with a mountain lion Kerry is found. Lassie leaves one of her offspring before continuing her journey.
Lassie's journey goes on, teaching the two pups about predators and survival in the wild. Taking shelter in an abandoned building during a storm, the adventuresome youngsters still find danger but Lassie keeps them safe.
Lassie and her remaining puppy meet a young teen Jodi Tyler in the forest. Living there with just her father, she has a special bond with animals. Lassie helps in a bulldozer accident then leaves her pup before continuing her journey.