In 1991, following the critical and commercial failure of her biography of Estée Lauder, author Lee Israel struggles with financial troubles, writer's block, and alcoholism. Her only friend is her cat, which has a health issue. Lee hopes to write a biography of comedian Fanny Brice, who died in 1951. Her literary agent Marjorie sharply rejects the idea, noting that Brice’s life no longer interests people. Marjorie explains that Lee, with her difficult personality, is responsible for her own career slump. With Marjorie unable to secure her an advance for a new book, regardless of subject matter, Lee resorts to selling her possessions to cover living expenses. She sells a personal letter she received long ago from Katharine Hepburn to a used bookstore merchant and autograph dealer named Anna. Lee begins spending time with old acquaintance Jack Hock after a chance encounter with him at a gay bar called Julius’. He reveals to her that he has been banned from all locations of the Duane Reade chain of stores because he was caught shoplifting. Lee visits a Manhattan library's special collections department to research Fanny Brice and discovers two letters typewritten by Brice. She removes one of them from the building, takes it to Anna's store, and shows it to her. Anna makes Lee an offer that is lower than what she was expecting, due to the letter's bland content. Lee returns home and uses a typewriter to add a postscript to the letter. Lee returns to the store where Anna, amused by what "Fanny Brice" wrote "several decades ago", offers Lee $350. Anna reveals to Lee that she has written some short stories and is soliciting advice about whether they are good enough to be published. The socially phobic Lee replies cautiously, as this is apparently the first time in many years that a woman has tried to befriend her and is asking for her help with getting something published. Lee uses some of the $350 Anna gave her to pay for veterinary treatment of her sick cat. The veterinary clinic previously had turned her and her cat away because of insufficient funds. Lee, emboldened by her success with selling the Brice letter, starts forging and selling letters supposedly written by deceased celebrities, incorporating intimate details to command high prices. Anna, a fan of Lee's biographies, tries to initiate a romantic relationship but may have another motive. On their dinner date, she gives Lee a manila envelope containing an original short story with the hope that Lee will critique it. Moments after they leave the restaurant, the socially phobic Lee appears to rebuff Anna. In some of Lee's letters, she has Noël Coward make references to his social life that reflects his homosexuality. A used-book dealer named Paul buys one of them from Lee and sends it to a friend of his who knew Coward. The recipient doubts Coward would have risked his privacy and relays his suspicions. Paul then raises an alarm that leads to Lee's customers blacklisting her. Unable to sell more forgeries, she has Jack sell them on her behalf, since the customers do not know he has a connection to Lee. She also starts stealing authentic letters from libraries and archives for Jack to sell, replacing them with forged duplicates. While Lee is out of town committing one such theft, she lets Jack stay in her apartment. He brings a young waiter from the gay bar Julius’ to join him there. Lee’s cat dies while under Jack’s care during the night he and the waiter spend together. Lee ends their friendship but continues their partnership out of necessity. The FBI arrests Jack while he is attempting a sale. He cooperates with them, resulting in Lee being served with a court summons. She retains a lawyer, who advises her to show contrition by getting a job, doing community service, and joining Alcoholics Anonymous. In court Lee says she enjoyed creating the forgeries but that her actions were ultimately not worth it because she lost her cat and her friendship with her criminal accomplice. He “may have been an idiot, but he tolerated me, and he was nice to have around.” The judge sentences Lee to five years' probation and six months' house arrest. During house arrest Lee skips her court-ordered AA meeting to meet with Jack, who is dying of AIDS, at the gay bar Julius’. They reconcile. Lee does not comment on or ask about his health. He grants her permission to write a memoir about their escapades. Sometime later, while Lee is passing a bookstore, she sees a Dorothy Parker letter she forged that is now on sale for $1,900. She writes the store owner a sarcastic note from the deceased Parker revealing that the letter is a fake. After reading the note, the owner goes to retrieve the letter but then decides to keep it on display.

On December 23, 1991, Cameron Todd Willingham awakes to find his house ablaze. Despite his best efforts, Willingham is unable to save the lives of his three daughters. At his trial, the prosecutor, John Jackson, reveals the fire had been caused deliberately, with gasoline spread in the shape of a pentagram and the refrigerator moved to block the kitchen door. Several witnesses portray Willingham as a violent individual. His former cellmate from when he was detained in jail, Johnny Webb, testifies that Willingham had told him the fire had been set deliberately. Despite Willingham and his wife Stacy protesting his innocence, he is sentenced to death. During his time on death row, Willingham is violently beaten and threatened by both inmates and guards before being placed in solitary confinement for his safety. There he breaks down, still protesting his innocence and having flashbacks to his life with Stacy. Willingham and Stacy are shown to have had a complicated relationship: she cheated on him, and he reacted violently toward her. But the two care for each other. Stacy stops replying to his letters at the insistence of her grandmother, who believes he is guilty. Willingham reaches out to a new lawyer, Reaves, in the hope of proving his innocence. He adapts to his life in prison by submitting to the violent guard Daniels and befriending fellow death row inmate, Ponchai James. During this time, Willingham improves his vocabulary and writing with James' help. The latter man is eventually executed. Willingham’s letter to Reaves ultimately reaches playwright Elizabeth Gilbert, who is sympathetic to his case. Her ailing ex-husband and their two children insist he is guilty. When Gilbert visits the prison, she is taken aback by his calm demeanor. The pair connect over their mutual struggles as parents and their love for their respective children. Willingham continues to immerse himself in art and poetry and befriends the guard Daniels. The guard starts to question Willingham's guilt after seeing him hallucinate about his daughters and reading his letters to Gilbert. Gilbert questions the witness statements and Reaves, who made no progress on the case in six years. She visits Webb, the former cellmate. When she questions him about prosecutor John Jackson paying him to lie about Willingham’s confession, he becomes agitated and threatens her. Willingham’s execution date is set, but she learns that more of the witnesses lied at the trial. Gilbert and Reaves meet with Dr. Hurst, who reveals the refrigerator had not been moved and that the fire could not have been arson, as the jury had been told and concluded. Despite this, Reaves is unable to argue an appeal, and Hurst’s report is disregarded. Webb recants his testimony, but Jackson covers this up. Stacy is pressured into lying that Willingham had confessed to her. Gilbert suffers a car crash as Willingham is taken to be executed. She is absent when he gives a poignant speech that shows the improvements he has made while on death row. He asks for his ashes to be spread over his daughters' graves. Daniels is selected to administer the lethal injection. Along with Stacy and Reaves, he tearfully watches Willingham die. Later, Gilbert, who was paralyzed from the crash, spreads Willingham’s ashes, attended by her own children present. In an epilogue and news footage, Texas Governor Rick Perry denies any guilt over ordering execution of inmates sentenced to death.

In May 1996, several commercial expeditions at the base camp of Mount Everest prepare to climb to the summit. Rob Hall, who popularized commercial Everest missions, leads Adventure Consultants; Scott Fischer is the chief guide for its rival, Mountain Madness. Rob's clients include Beck Weathers, an experienced climber; Doug Hansen, a former mailman pursuing his dream; climbing veteran Yasuko Namba, who hopes to complete her final Seven Summits ascent; and Outside magazine journalist Jon Krakauer. Helen Wilton manages Rob's base camp. A month earlier in New Zealand, Rob says goodbye to his pregnant wife Jan, promising he will be home for the birth. At the base camp, Rob receives a fax from her, informing him that their unborn baby is a girl. He wants to name her Sarah, but she disagrees. Worried about climbers overcrowding, Rob persuades Scott to cooperate to reduce delays. On the summit attempt, Rob's group departs from Camp IV before dawn, planning to complete the ascent and begin descending by 2:00 PM., the latest safe time to ensure return before nightfall. The group is delayed by over an hour after discovering that guide ropes are not installed on the upper reaches of the climb. Beck has eyesight problems and stops. Rob tells him to return to base camp if his condition does not improve in a half-hour. Scott hurries down to camp to help another climber but plans to re-ascend, and Rob warns him about overexertion. Rob reaches the summit on time and is joined by other climbers including Yasuko, who jubilantly plants her Japanese flag. Descending, Rob encounters Doug struggling to ascend just above the Hillary Step and orders him to descend. Doug insists on continuing, saying that he will not get the chance again. Rob reluctantly agrees and they reach the summit two hours later, well past the safe return time. Doug is exhausted and suffering from altitude sickness. With them is Scott, exhausted and ill from high-altitude pulmonary edema. As Rob helps Doug descend, a blizzard strikes while Doug's oxygen tank is empty, causing him to suffer hypoxia. No extra bottles are stored on the route as Rob asked and he radios Helen to send more oxygen. Doug, left briefly by Rob, semi-consciously detaches himself from the guide rope and walks unsteadily along the narrow path, then silently topples to his death. Scott's condition worsens. He tells his fellow climbers to continue descending without him. He lies down and later dies. Descending climbers reach Beck, whose vision remains impaired, but they all become lost as the blizzard obliterates the trail. Three climbers go for help, leaving Beck and Yasuko. Guide Andy 'Harold' Harris reaches Rob with spare oxygen, but the cylinder aperture is frozen shut. They huddle together in the storm. While Rob sleeps, Andy begins to have hallucinations. He then strips off his outer clothing and slides to his death. In the morning, Rob radios Helen that Doug and Andy are gone and that his extremities are frozen. Helen calls Jan, hoping that Rob will respond to her voice. Jan tells him that he must start moving. Rob tells her that he is cold but otherwise comfortable, and asks her to name their baby Sarah, dying soon afterward. Returning climbers tell the camp that Beck and Yasuko are stranded. The weather, however, makes a rescue impossible. Helen calls Beck's wife Peach, informing her of the situation. In the morning, Beck miraculously awakens, sees that Yasuko is dead, and stumbles down to camp alone, severely frostbitten and in need of medical help. Peach calls the American Embassy and organizes a helicopter rescue. Nepal Army pilot Lt. Col. Madan Khatri Chhetri flies a high-altitude mission to take Beck to the hospital. Meanwhile, one of Scott's guides, Anatoli Boukreev, finds his body and moves it off the trail. Returning home, Helen has an emotional reunion with Jan, who later gives birth and names her daughter Sarah. Beck returns to his family, heavily bandaged. Closing titles reveal that he eventually lost both hands and nose to frostbite and that Rob's body (as well as those of the other climbers who died) remains on Everest.

The film begins with an interview of the older Roger Sharpe, with flashbacks to 1971.

Occupational therapist Dian Fossey is inspired by anthropologist Louis Leakey to devote her life to the study of primates. She writes ceaselessly to Leakey for a job cataloging and studying the rare mountain gorillas of Africa. Following him to a lecture in Louisville, Kentucky in 1966, she convinces him of her conviction. They travel to the Congo, where Leakey and his foundation equip her to make contact with the gorillas, and introduce her to a local animal tracker, Sembagare. Settling deep in the jungle, Fossey and Sembagare locate a troop of gorillas, but are displaced by the events of the Congo Crisis and forcibly evicted from their research site by Congolese soldiers, who accuse Fossey of being a foreign spy. Fossey is resigned to returning to the United States, but Sembagare and her temporary host Rosamond Carr motivate her to stay in Africa. Fossey establishes new research efforts in the jungles of neighboring Rwanda, where rampant poaching become apparent when she discovers several traps near her new base at Karisoke. Nevertheless, Fossey and her colleagues make headway with the gorillas, taking account of their communication and social groups. Her work impresses Leakey and gains international attention. National Geographic, which funds her efforts, dispatches photographer Bob Campbell to highlight her research. Fossey, initially unreceptive, grows increasingly attached to Campbell after several photo sessions with the gorillas, and the two become lovers, in spite of Campbell's marriage. Campbell proposes to divorce his wife and marry Fossey but insists that she would have to spend time away from Karisoke and her gorillas, leading her to end their relationship. Fossey forms an emotional bond with a gorilla named Digit, and attempts to prevent the export of other gorillas by trader Van Vecten. Appalled by the poaching of the gorillas, Fossey complains to the Rwandan government and is dismissed, but a government minister promises to hire an anti-poaching squad. Fossey's frustrations reach a climax when Digit is beheaded by poachers. She leads numerous anti-poaching patrols, burns down the poachers' villages, and even stages a mock execution of one of the offenders, serving to alienate some of her research assistants and gaining her various enemies. Sembagare expresses concern at Fossey's opposition to the emergent industry of gorilla tourism, but she nonchalantly dismisses his worries. On Boxing Day, 1985, Fossey is murdered in the bedroom of her cabin by an assassin with a machete. At a funeral attended by Sembagare, Carr, and others, she is buried in the same cemetery where Digit and other gorillas had been laid to rest. Sembagare symbolically links the graves of Fossey and Digit with stones as a sign that their souls rest in peace together before leaving. An epilogue text explains that Fossey's actions helped save the gorillas from extinction, while her death remains a mystery.