In 1925 Lynchburg, Virginia, young Desmond Doss nearly kills his brother during roughhousing. That event and his Seventh-day Adventist upbringing reinforce Desmond's belief in the commandment "Thou shalt not kill." Fifteen years later, Doss takes an injured man to the hospital and meets a nurse, Dorothy Schutte. They strike a romance, and Doss tells Dorothy of his interest in medical work.

After the Japanese attack on Pearl Harbor brings the United States into World War II, Doss enlists in the United States Army to serve as a combat medic. His father, Tom, a First World War veteran, is deeply upset by the decision. Desmond and Dorothy get engaged.

Doss is placed in basic training under the command of Sergeant Howell. He excels physically but becomes a pariah among his fellow soldiers for refusing to handle a rifle and train on Saturdays. Howell and Captain Glover attempt to discharge Doss for psychiatric reasons under Section 8 but are overruled, as Doss's religious beliefs do not constitute mental illness. They subsequently torment Doss by putting him through grueling labor, intending to drive Doss out. Despite being beaten one night by his fellow soldiers, he refuses to identify his attackers.

Doss's unit completes basic training and is released on leave during which Doss intends to marry Dorothy, but his refusal to carry a firearm leads to an arrest for insubordination. Captain Glover and Dorothy visit Doss in jail and try to convince him to plead guilty so that he can be released without charge, but Doss refuses to compromise his beliefs. At his court-martial, Doss pleads not guilty, but before he is sentenced, his father barges into the tribunal with a letter from his former commanding officer (now a brigadier general) stating that his son's pacifism is protected by the US Constitution. The charges against Doss are dropped, and he and Dorothy are married.

Doss's unit is assigned to the 77th Infantry Division and deployed to the Pacific Theater. During the Battle of Okinawa, Doss's unit will relieve the 96th Infantry Division, which was tasked with ascending and securing the Maeda Escarpment ("Hacksaw Ridge"). During the initial fight, with heavy losses on both sides, Doss saves the life of his squadmate Smitty, earning his respect. As the Americans camp for the night, Doss reveals to Smitty that his aversion to holding a firearm stems from nearly shooting his drunken father, who threatened his mother with a gun. Smitty apologizes for doubting his courage, and both reconcile.

The next morning, the Japanese launch a massive counterattack and drive the Americans off the escarpment. Smitty is killed, and Howell and several of Doss's comrades are left injured on the battlefield. Doss hears the cries of dying soldiers and returns to save them, carrying the wounded, and Smitty's body, to the cliff's edge and belaying them down by rope, each time praying to save one more. The arrival of dozens of wounded who had been presumed dead comes as a shock to the rest of the unit below. When day breaks, Doss rescues Howell, and both escape Hacksaw under enemy fire.