The Stratton kids, Samantha and Chip, and their grandmother, Ada, drive to visit their Uncle Stuart. Grandma collapses and dies in a strange town, leaving the kids and Lassie on their own.
| Actor | Role |
|---|---|
 Sally BoydenSamantha Stratton | Samantha Stratton |
| SShane SinutkoChip Stratton | Chip Stratton |
 John ReillyStuart | Stuart |
 David WayneAmos | Amos |
 Gene EvansSheriff Marsh | Sheriff Marsh |
 Lee BryantKathy | Kathy |
 Jeff HarlanBuzz | Buzz |
 Jeanette NolanAda Stratton | Ada Stratton |
 John McIntireDr. Spreckles | Dr. Spreckles |
 Jim AntonioMr. Waldrup | Mr. Waldrup |
 Logan RamseyFlannagan | Flannagan |
 Lucille BensonJuno | Juno |
| HHelen Page CampMiss Tremayne | Miss Tremayne |
 Woody ChamblissVictor Turkey | Victor Turkey |
 James CrittendenMitch | Mitch |
 Shelley MorrisonLena | Lena |
| JJohn O'LearyJerry Bergan | Jerry Bergan |
 Fred PinkardSgt. Lewis | Sgt. Lewis |
| DDanil TorppeRon | Ron |
 Charles TynerAsa Bluel | Asa Bluel |
 Gwen Van DamMrs. Waldrup | Mrs. Waldrup |
 Ned WertimerLeroy Aames | Leroy Aames |
| FFrank WhitemanOfficer Ken | Officer Ken |
 LassieLassie the Dog | Lassie the Dog |