In June 1995, despite a lack of hiking experience, Cheryl Strayed leaves Minneapolis to hike, by herself, 1,100 miles (1,800 km) of the 2,650-mile (4,260 km) Pacific Crest Trail. During the journey, she reflects on her childhood and memories of her mother, Bobbi, whose death from cancer sent Cheryl into a deep depression that she tried to numb with heroin and anonymous sex. After her behavior destroyed her marriage and then led to an unwanted pregnancy, Cheryl had an abortion and resolved to hike the trail to try to rediscover the woman her mother raised her to be.
Cheryl begins her trek in the Mojave Desert in Southern California. On the first night, she discovers she brought the wrong type of fuel for her stove and is therefore unable to cook. After a few days of eating only cold food, she meets a farmer named Frank, who feeds her and takes her to get the correct fuel.
Further along the trail, Cheryl meets a hiker named Greg, who agrees to help her plan the next section of her hike when they get to Kennedy Meadows. While she is there, a camper named Ed helps her strategically lighten her overweight backpack and arrange to replace her undersized hiking boots with a new pair, which will be delivered somewhere further along the trail. At this and various other stops, Cheryl's best friend Aimee sends her provisions, and she also receives letters from her ex-husband Paul, who still cares about Cheryl, congratulating her on her progress.
Cheryl takes Greg's advice to avoid some upcoming deep snow in the Sierra Nevada by catching a bus to Reno and rejoining the PCT, deciding to extend her trip further into Oregon so she can walk the same distance as she had planned, but she still encounters quite a bit of snow. She is able to make it through and arrives at the town where her new boots were sent, though she has to walk the last 50 miles in sandals reinforced with duct tape after she accidentally knocks one of the small boots down a steep slope.
An empty water tank in the desert beyond the town leads Cheryl to go without water for a full day in extreme heat before, dehydrated and near exhaustion, she finds a muddy puddle from which she can get potable water using her portable water purifier. While she waits for the water to disinfect, two hunters approach and make suggestive remarks, leaving Cheryl feeling threatened and vulnerable. One returns later in the day, but leaves when his friend calls for him, so Cheryl runs until she is sure she is not being followed.
Cheryl crosses into Oregon and goes to Ashland. She meets Jonathan, who invites her to a tribute concert to the recently-deceased Jerry Garcia, and they spend the night together.
Sometime later, after visiting Crater Lake, Cheryl gets to Mount Hood National Forest, where she encounters a friendly group of young male hikers who recognize her from the brief quotes and poems that she frequently writes alongside her signature in the hiker's record books along the PCT.
One rainy day, Cheryl finds a llama that escaped from a young boy hiking with his grandmother. She returns it and chats with the boy, who asks about her parents. When she mentions her mother is dead, the boy sings her "Red River Valley", which his mother used to sing to him. The boy and his grandmother carry on down the trail, and Cheryl breaks down and cries.
On September 15, after 94 days of travel, Cheryl reaches the Bridge of the Gods on the Columbia River between Oregon and Washington, ending her journey. At various points along the trail, including at the bridge, she has encountered a red fox, which she interprets as being the spirit of her mother watching over her. As she walks onto the bridge, her future-self reflects, via voice-over, on what she learned from her trip, and reveals that four years later she remarried at a spot near the bridge, nine years later she had a son, and a year later, a daughter, who she named Bobbi, after her mother.
