A hawk Lassie rescues from entanglement in kite string returns the favor when the coyote pup Lassie has befriended is threatened by a snake. But it's Lassie herself who then must be rescued by Ron Holden and Dale Mitchell, two young men on a hiking trip, after she must save the hapless pup from nearby rapids.
Now accompanied by Lassie, Ron and Dale have the gold they have been placer mining assayed--and just for the heck of it, buy an old treasure map and go in search of a gold mine. Once they find the place, however, their search is endangered by fire heading for some old dynamite left in a shed.
Lassie befriends a trouble-prone mutt who is mascot of an old railroad spur line.
The boys and Lassie sleep in an old barn that appears to be haunted.
Ron and Dale return to the Holden Ranch, where Lassie is welcomed by Garth Holden and his foster sons, boys who have been orphaned or abandoned by their families.
Mike, the new boy, begins works at the local animal clinic and developes a crush on the veterinarian,he's also feeling shy until he helps nurse an injured owl back to health.
While in town picking up a gift for Garth, Ron is knocked unconscious when an earthquake strikes, and when he comes to, Lassie has escaped from the truck. As he and the dog search for each other, Lassie helps fellow animals dislocated by the quake, and Ron enlists his father in the search.
Ron and Lassie return home from a trip to find Mike has adopted a raccoon from the wild animal park--and ""Rags"" is immediately jealous of Lassie. Soon dog and raccoon are embroiled in a feud, endangering both of them on a house construction site.
Mike befriends Henry Newton, who flies a Curtis Pusher at airshows under the name ""The Flying Grandpa,"" when his aircraft breaks down in the Holden pasture. His long involved tall tales of bravery during air feats impress the boy, but bother Garth, who thinks Newton's lies might backfire. And when a bear charges Newton and Mike, the elderly man finds out they do.
Garth and Dale survey rangeland for the Forest Service and see a young white stallion challenging the older black leader of a horse herd; Garth predicts the white horse will soon succeed. When he does, driving the injured black stallion away from water, Lassie tries to lead him to safety before he collapses.
As Lassie gently leads the stallion back to the Holden Ranch, Garth and Dale leave food and drink for the animal, hoping he will choose himself to live at the ranch.
Ron and Dale, home from college, go out on the annual stray roundup and make a bet on which of them will find the most cattle. But it's Lassie who gets the jump on them, helps a calf stuck in quicksand, and then must help Ron when he's thrown from his horse.
Ron and Dale, spending two days camping at Pine Lake before returning to college, pick up a boy that Dale can tell is ""on the run."" Sure enough, once he leaves them he builds a campsite in the woods. When the boys find his camp in the woods, he steals one of the motorcycles they've rented.
Garth takes Lassie with him on his visit to Vandenberg Air Force Base, where they meet Jimmy Fredericks, a boy with a weakened leg who has given up believing he will ever walk normally.
Lassie protects a snow goose who has chosen to lay her eggs on the flightline.
Lassie befriends a diabetic poodle named Sparky who stows away on the Looking Glass, where there's no insulin, to be with his owner.
Jimmy finds out that his father's flight may crash and must re-examine his faith.
Hoping to help his self-esteem, Garth takes Jimmy back to the ranch with him. There the uncertain boy meets Lucy Baker, a girl who's been deaf most of her life, and her pet wolf Mountie. But while Jimmy and Lucy get to know each other, Mountie, playing with Lassie, is shot by a shepherd who doesn't know he's a pet.
After Lucy and Jimmy find Mountie in the cave where Lassie has hidden him, Lucy sends Jimmy for help on her horse. He is frightened to do so, but does so for her sake, and despite being thrown, finds Domenic, the shepherd who shot Mounty. Meanwhile, Lassie returns to the ranch.
When Mountie weakens and then dies, even normally optimistic Lucy cannot understand and sinks into depression, so Sue asks her to help out at the wild animal park to take her mind off her loss. Eventually Lucy begins taking an interest in the animals, including a llama about to give birth.