- Reese Witherspoon as Cheryl Strayed[5]
- Bobbi Strayed Lindstrom (daughter of the real-life Cheryl Strayed) as Cheryl (6 Yrs Old)[6]
- Laura Dern as Barbara "Bobbi" Grey, Cheryl's mother[7]
- Thomas Sadoski as Paul, Cheryl's ex-husband[7] (based on Marco Littig, the real-life Cheryl's ex-husband)
- Michiel Huisman[8] as Jonathan, a man Cheryl has sex with after meeting him in Ashland, Oregon
- Gaby Hoffmann[8] as Aimee, Cheryl's best friend in Minnesota
- Kevin Rankin[8] as Greg, a hiker Cheryl meets on the trail who ends up quitting (based on Roger Carpenter)
- W. Earl Brown[8] as Frank, a farmer who lets Cheryl eat, shower, and sleep at the home he shares with his wife, Annette
- Mo McRae as Jimmy Carter, a reporter who interviews Cheryl for the "Hobo Times" after mistaking her for a hobo drifter
- Keene McRae as Leif, Cheryl's younger brother[9]
- Brian Van Holt as the Ranger in Mount Hood National Forest who reopens the station for Cheryl and brings her breakfast
- Cliff DeYoung as Ed, a man at Kennedy Meadows trail stop who helps Cheryl
- Ray Buckley (credited as Ray Mist) as Joe, Cheryl's drug-addicted boyfriend who got her pregnant, resulting in an abortion
- Randy Schulman as the Therapist that Cheryl sees after Bobbi's death
- Cathryn de Prume as Stacey Johnson, a female hiker Cheryl meets at a stop on the trail
- Charles Baker as T.J., the more threatening of a pair of hunters Cheryl meets on the trail
- J.D. Evermore as Clint, the less threatening of a pair of hunters Cheryl meets on the trail
- Beth Hall as the Desk Clerk at the motel where Cheryl stays before beginning her hike
- Jan Hoag as Annette (Frank's Wife)
- Art Alexakis as the Tattooist
- Anne Gee Byrd as Vera, a woman Cheryl meets on the trail; Kyle's grandmother
- Evan O'Toole as Kyle, a young boy Cheryl meets on the trail; Vera's grandson
- Jason Newell as Cheryl's Dad (Ronald Nylund)
Cheryl Strayed makes a cameo appearance at the beginning of the film as the woman who drops off the character of Cheryl at the motel where she stays before beginning her hike.
