Nazis used gas chambers to murder the majority of concentration and death camp prisoners, especially Jews. The most famous gas chambers were built at the largest death factory, Auschwitz II, Birkenau. All told, four of these killing factories were built at the massive camp. Up to 2,000 persons could be killed at once in one chamber.

Concentration camp expert Wolfgang Sofsky, whose book "The Order of Terror" provides one of the clearest accounts of how the system functioned, describes how the gas chambers figured prominently in that process: "A death factory is a work organization whose purpose is the annihilation of large numbers of human beings, without a trace. On a twenty-four-hour basis, victims were murdered, their corpses displosed of. Kommandos of prisoners collected the belongings of the dead and brought them to the sorting sites. The bodies were checked for gold teeth and thrown into mass graves or pits or burned in cremation ovens. Mass annihilation was organized on the basis of a division of labor. The process was integrated into a kind of assembly line, its stations coordinated in temporal sequence. Killing was mechanized by the installation of stationary gas chambers, into which hundreds of persons were lured and then poisoned by carbon monoxide or hydrocyanic acid fumes. The death factory was an apparatus that functioned smoothly, virtually trouble-free, working at a high capacity and speed. A death train arrived at the ramp in the morning; by the afternoon, the bodies had been burned, and the clothing brought to the storerooms."

At Auschwitz and Majdanek, Nazis employed Zyklon B, a crystalline hydrocyanic acid that became poisonous gas when released into the gas chamber vents. Nazis first experimented with the gas in Block 11 at Auschwitz I, where 600 Soviet POWs and 250 Poles were killed in Sept 1941 with Zyklon B. Rudolf Höss, the camp commandant, reported the experiment provided him the mental comfort he needed for implementing mass murder: "I will say frankly that killing that group of people by gas relieved my anxieties. It would soon be necessary to start the mass extermination of the Jews, and until that moment neither I nor [Adolph] Eichmann had known how to conduct a mass killing. A sort of gas was to be used, but it was not known what kind of gas was meant and how to use it. Now we had both the gas and the was of using it. I had always been concerned at the though of mass shootings, particularly of women and children. I was already sick of executions. Now my mind was at ease."

At the Chelmno death camp and a subcamp Gusen, mobile gassing vans used carbon monoxide exhaust to kill prisoners, while the "Action Reinhard" camps (Sobibor, Treblinka, Belzec) used carbon monoxide gas chambers.