In autumn of 1944, at Auschwitz-Birkenau III, the Fourth Sonderkommando, a small group of Jewish prisoners assigned as laborers in the camp, oversees a load of Jewish prisoners bound for the gas chambers. The kommando's job is to ready the doomed Jews for death, ordering them to undress, turn over their valuables and herding them into the gas chambers where they are killed with Zyklon-B.
The kommando enjoys privileges that are unheard of among Jews during World War II: they enjoy good food, are given decent living quarters and are even allowed to keep valuable articles taken from prisoners who are gassed. They are also only allowed to work for the camp for four months before being exterminated. One of the kommando, an old man, is near death and Dr. Miklos Nyiszli, a Czech Jew, is called from the Medical Experimentation block (where he works under the supervision of Joseph Mengele) by Hoffman, to tend to the old man. He revives the man but is thwarted by another prisoner, Rosenthal, who suffocates the old man with his pillow. The man's body is taken away to the crematoria where it will be incinerated.
Nyiszli himself meets with Mengele and informs the notorious SS doctor that the experiments he's been ordered to perform on Jewish prisoners are too much for him to complete alone. Mengele says he'll provide Nyiszli with more staff. Mengele also grants Nyiszli permission, for his exemplary work, to visit his wife and daughter at the women's block of the camp.
Speculation exists among the kommando that they will be liquidated by the camp command within a week. The kommando has been secretly receiving supplies for an uprising: local Poles from the countryside have been smuggling the prisoners gunpowder, grenades, ammunition and rifles for several months. The plan is to detonate a large bomb in Crematoria 4, rendering it unusable. The women of the camp, who have been working at the UNIO munitions factory have also been smuggling the men supplies for combat. Two in particular, Dina and Rosa, are discovered, separated and cruelly tortured for information about their plans. Rosa is killed by the SS of the camp and her body is left in Dina's room while she awaits further interrogation.
While pulling the bodies of an exterminated group of Jews apart in the gas chamber, Hoffman finds a young girl who survived the gassing. He takes her out and manages to get her body sent past the crematorium by claiming she's a twin & would be a suitable experimental subject for Dr. Mengele. Dr. Nyiszli is called in to revive the girl fully. Due to shock, she is unable to speak. The kommando plans to help her escape the camp or to have her moved to the woman's camp where she may survive.
Dina's entire barracks is taken out to a courtyard where they are summarily executed one at a time while she watches. She refuses to reveal the plans of the uprising and throws herself into an electrified fence where she dies.
One of the German commandants, SS-Oberscharfuhrer Muhsfeldt, has been ordered by his superiors to investigate if the women's smuggling has infiltrated the men's camp. Muhsfeldt discovers the kommando hiding the girl in their washroom and, using her as leverage, interrogates the prisoners about the stolen and secreted arms. Dr. Nyiszli orders the rest of the kommando out of the room and privately tells Muhsfeldt about the uprising, though he cannot tell him the precise date and time. Muhsfeldt muses on how easily the Jews of Europe were defeated by the Nazis and how easily they were used for forced labor. He also talks of their plans to exterminate the rest of the kommando by the end of the month.
The uprising begins the afternoon of October 7th. The bomb is exploded in Crematoria 4, destroying it beyond repair. The kommando holds out for several hours but are eventually overrun and captured. The ringleaders are rounded up and made to sit outside the ruined crematoria while the fires are extinguished. All of them are eventually made to lie face down on the grass while they are shot in the head one at a time. Hoffman and his fellow kommando, Rosenthal, talk about how they both grew up in the same town and would've been neighbors if they survived the war and returned home. They hold hands as the SS officer shoots them both.
The girl who survived the gas chamber is allowed to witness the mass execution and is then allowed to run for a nearby gate, seemingly set free. Muhsfeldt, an expert marksman, draws his pistol and shoots her dead. A monologue by the girl plays over her cremation and she talks of being expelled as ashes into the air and river where the ashes of all the cremated prisoners are dumped by the Nazis.