In the future on a human-populated space colony, Nova Prime, the S'krell extraterrestrial race attempts to take it over with creatures called Ursas, which hunt by "sensing" fear despite being technically blind. Humanity created a peacekeeping military organization, The Ranger Corps, to fight the threat. Their leader, General Cypher Raige, defeats the Ursas with a fear-suppressing technique he called "ghosting". Cypher's daughter, Senshi, was killed during an Ursa assault. Blaming himself for his sister's death, Senshi's 14-year-old brother Kitai trains to become a Ranger like Cypher but is rejected. Kitai's mother Faia convinces Cypher to take their son on his last mission before he retires. He takes The Ranger Corps off planet to train with a live Ursa, which is tied and immobilized in their spaceship. During flight, the ship is caught in an asteroid shower, causing them to crash-land on Earth, now a desolate and uninhabited planet which humans had evacuated a thousand years earlier due to an environmental cataclysm. Cypher and Kitai survived the crash, but Cypher's legs are broken, and the main beacon for firing a distress signal is damaged. Cypher instructs Kitai to locate the tail section of the ship, which broke off on entry to the atmosphere. Inside is the backup beacon, which they can use to signal Nova Prime. Cypher gives Kitai his weaponized cutlass, a wrist communicator, and six capsules of a fluid that enhances oxygen intake so he can breathe. Kitai leaves to find the tail section, with Cypher guiding him through the communicator. Kitai confronts many hazards; bitten by a paralytic leech after fleeing from a pack of baboon-like monkeys, he self-medicates but damages two of his capsules. After awakening, Kitai takes shelter just as the thermal shift arrives, where Cypher tells him a story about how he conceived "ghosting" to kill the Ursas. Kitai reaches a cliffside waterfall, and Cypher learns about the broken capsules. Knowing that the only way to continue with two capsules would be to skydive, Cypher orders Kitai to abort the mission, but Kitai, believing that his father sees him as a disappointment, refuses to comply after blaming Cypher's absence at home for Senshi's death. Kitai disobeys Cypher's order and skydives down the waterfall but is captured by a large eagle, and his communicator is damaged. In the eagle's nest, Kitai fails to defend her chicks against large panthers before escaping to a river, where he drifts on a raft and a thermal shift nearly freezes him to death. The eagle, who had been following him, shelters Kitai, sacrificing her life. Kitai reaches the tail section and learns that the ship's Ursa has escaped and killed the rest of the crew. He tries to activate the emergency beacon, but the atmosphere blocks the signal. He climbs up the volcano where he hopes the high altitude will help to activate the beacon, but he encountered the loose Ursa, and it attacks him. Kitai kills it using the "ghost" technique he learned from Cypher. After activating the beacon, he and Cypher are sent back to Nova Prime via a rescue team.

After living in the UK for ten years, author Bill Bryson has moved back to the US and is living in New Hampshire. Now in his 60s, he has been living there peacefully. A television interview reports that he has published several popular books and there is speculation he will be writing more. Bryson, however, has no such plans. Bryson and his wife Catherine attend a funeral. Afterwards, he takes a stroll up to the nearby Appalachian Trail, and suddenly decides he will hike its entire length. Catherine objects, presenting many accounts of accidents and murders on the trail. She relents on the condition that he not travel alone. He agrees and searches for a friend willing to join him. Everyone declines his invitation; some declare him insane. Finally, he is contacted by Stephen Katz, an old friend who offers to be a hiking companion. Despite appearances, Stephen claims to be fit enough for the challenge. Bill's wife is unhappy with his choice, but relents. Within less than a mile of their departure point, as groups of hikers overtake and pass them, they begin to grasp the difficulty of their ambition. Shortly after, a group of young children effortlessly runs by them up the trail, laughing and calling out to each other. Seeing others pass by so easily motivates them to carry on. Weeks pass, and they overcome obstacles and encounter interesting characters together, some friendlier and some more hostile. One day, having hiked miserably through pouring rain, they reach a hut. Carved into the log wall is an Appalachian Trail map showing the trail and their present location. They realize they have finished less than half of the trail after spending three months on it. The two ultimately trek into a restricted section posted "for experienced hikers only". While maneuvering their heavy and awkward backpacks alongside a precipitous drop, Bill trips and pulls Stephen with him down a steep, rocky cliff. They fall about fifteen feet onto a ledge spacious enough to be comfortable, but far enough below the trail to be unable to get back up to resume the hike. They spend the night there with no clear hope of rescue. The next day, they are awakened by early morning hikers who are able to get them off the ledge. The men decide they have had enough and end their journey. When comfortably back at home, Bill, going through his mail, finds a series of postcards from Stephen that were mailed from their various stops along the trail. The last one reads: "What's next?' Bill sits down and begins typing on his computer, " A Walk In The Woods."

In the 2000s, Amanda is an aimless 25-year-old Italian woman who feels alienated from her wealthy family—particularly her mother and her older sister—and struggles to form meaningful social connections after finishing school in Paris. Despite having the opportunity to work in her family's pharmacy business, she instead spends her time wandering the city, frequenting the local cinematheque and raves in search of friends, trying to forge online connections via video chat rooms while staying in a hotel room funded by her parents, and visiting an aging horse tied up at a nearby farm. At her mother's suggestion, Amanda visits Rebecca, the daughter of her mother's friend Viola and a childhood friend she has not seen for many years. A former athlete, Rebecca lives a reclusive life, rarely leaving her room and regularly attending psychotherapy sessions at home. After Rebecca slams her bedroom door on Amanda without saying a word, Amanda learns from Viola that she and Rebecca were inseparable as toddlers before Amanda's family moved away. Convinced that she and Rebecca could have been best friends all along, Amanda becomes determined to rekindle their friendship. After Amanda repeatedly tries to force her way into Rebecca's room, Rebecca finally lets Amanda in and they warm up to each other. At a rave, Amanda meets a boy whom she suspects is a drug dealer, but he clarifies he hands out free condoms at raves. The two go out to eat and become acquainted, after which Amanda saves his contact as "My Boyfriend" on her phone. When the boy invites Amanda to his upcoming birthday party, telling her she can bring someone, she invites Rebecca to accompany her. As the two girls continue to spend time together, Amanda moves in temporarily with Rebecca, though Amanda becomes jealous of Rebecca's therapist, Ann. The boy from the rave tells Amanda to stop texting him incessantly as he is dating another girl, leaving her heartbroken. Back at Rebecca's house, Ann instructs Amanda to tell Rebecca that she is leaving for Paris, before declaring that Amanda's borderline personality traits are not good for Rebecca. In despair, Amanda flees, steals the horse and returns to Rebecca's house with the horse, leaving it in the garden. She then goes to Rebecca's room and tries to persuade her to run away with her, but Rebecca agrees with Ann's assessment and reveals that Viola made Rebecca befriend Amanda when they were children because everyone felt sorry for Amanda. Devastated, Amanda leaves. Amanda moves back into her family's villa, and her relationship with her mother and sister gradually improves. Viola approaches Amanda, asking her to reunite with Rebecca. Amanda tells Viola that Rebecca can find her at the local cinematheque, but Rebecca never shows up. Later, the boy from the rave accuses Amanda of crashing his party the previous night and setting off firecrackers in his living room, but she denies it. Realizing that this was Rebecca's doing, Amanda goes to her house and thanks her. Rebecca confesses that she rode to the party on horseback, but the firecrackers scared off the horse. Amanda and Rebecca set off in search of the horse, suggesting a tentative reconciliation.

On November 30, 1962, a month after the Cuban Missile Crisis, George Falconer is a middle-aged English college professor living in Los Angeles. George dreams that he encounters the body of his longtime partner, Jim, at the scene of the car accident that took Jim's life eight months earlier. He bends down to kiss his dead lover. After awakening, George delivers a voiceover discussing the pain and depression he has endured since Jim's death and his intention to end his life that evening. George receives a phone call from his dearest friend, Charley, who projects lightheartedness despite also being miserable. George goes about his day putting his affairs in order and focusing on the beauty of isolated events, believing he is seeing things for the last time. At times, he recalls his sixteen-year-long relationship with Jim. During the school day, George comes into contact with a student, Kenny Potter, who shows interest in George and disregards conventional boundaries of student–professor discussion. George also forms an unexpected connection with a Spanish male prostitute, Carlos. That evening, George meets Charley for dinner. Though they initially reminisce and amuse themselves by dancing, Charley's desire for a deeper relationship with George and her failure to understand his relationship with Jim angers George. George goes to a bar and discovers that Kenny has followed him. They get a round of drinks, go skinny dipping, and then return to George's house and continue drinking. George passes out and wakes up in bed with Kenny asleep in another room. While watching Kenny, George discovers that he has fallen asleep holding George's gun to keep George from killing himself. George locks the gun away, burns his suicide notes and in a voiceover explains that he has rediscovered the ability "to feel, rather than think". As he makes peace with his grief, George suffers a heart attack and dies, while envisioning Jim appearing and kissing him.