In late 1941 a large number of Soviet POWs arrived. This was the first group to be gassed in the gas chambers, early in 1942. Previously, exhausted prisoners were transferred to Schloss Hartheim, where gas chambers had operated since 1940.

Also, many Austrian Jehovah's Witnesses were put into concentration camps during this period. The book Die Geschichte des Konzentrationslagers Mauthausen (The History of Mauthausen Concentration Camp, documented by Hans Maršálek, Vienna, Austria, 1974), which has a preamble by Franz Jonas, former president of the Austrian Federal Republic, says: "There existed a group of people in Mauthausen Concentration Camp who were persecuted on religious grounds only: members of the sect ‘Earnest Bible Students,’ or ‘Witnesses of Jehovah’ . . . Their rejection of the loyalty oath to Hitler and their refusal to render any kind of military service—a political consequence of their belief—were the reason for their persecution".

In 1944 a large group of Hungarian and Dutch Jews was also transferred. Most of them either died as a result of the hard labour and poor conditions, or were thrown down the sides of the Mauthausen quarry (nick-named the Parachute Wall by the SS guards). During the final months of the war, some 20,000 prisoners from other concentration camps were marched to the complex. Before and during World War II large groups of Spanish Republicans were also transferred to the camp and its sub-camps.

The estimated number of prisoners that passed through all of the sub-camps is 335,000; most of them were forced to do hard labour in a rock quarry. The rock quarry was at the base of the infamous "stairs of death". Prisoners were forced to carry blocks — often weighing as much as 50 kilograms — up the 186 stairs, one behind the other. As a result, many times exhausted prisoners would collapse in front of the other prisoners in the line, and fall on top of those prisoners, creating a horrific domino effect — that is, the first prisoner falling into the next, and so on all the way down the stairs.

Such brutality was not uncommon. In fact, often times, the SS guards would force prisoners — exhausted from hours of hard labour and insufficient food and water — to race up the stairs with the blocks. Those who survived the ordeal would often be placed in a line-up at the edge of a cliff known as "The Parachute Jump". At gunpoint, each prisoner would have the option of being shot, or pushing the prisoner in front of them off of the cliff. In all, some 122,000 were murdered, although the surviving German camp files noted only 71,000 victims. The living conditions were extremely squalid; all were undernourished, and diseases without proper medical attention caused many deaths.

A women's camp opened in Mauthausen in September 1944 with the first transport of female prisoners from Auschwitz. Eventually more women and children came to Mauthausen from Ravensbruck, Bergen Belsen, Gross Rosen, and Buchenwald. With them came some female matrons. Twenty are known to have served in the Mauthausen camp, sixty in the whole camp complex. Female guards also staffed the Mauthausen subcamps at Hirtenberg, Lenzing (the main women's subcamp in Austria), and St. Lambrecht. Chief wardress at Mauthausen was first Margarete Freinberger, then Jane Bernigau. Of all the female overseers who served in Mauthausen, almost all of them were recruited between September 1944 and November 1944 from Austrian cities and towns. One female guard came from Schwertberg, a small village located only some miles from the Mauthausen concentration camp. Edda Scheer, who worked in a factory in Hirtenberg, Austria was recruited by force in September 1944 and sent to Ravensbruck for Aufseherin training. Soon after she was sent to the Hirtenberg subcamp near Vienna, Austria. When the SS evacuated the camp in April 1945 Edda came to Mauthausen. After the war she stated about the main camp at Mauthausen, "Every now and then [we] drove the prisoners to the crematorium because one did always die somewhere." She was never punished for war crimes. In erly April 1945, atleast 2,500 more female prisoners came from the female subcamps at Amstetten, St. Lambrecht, Hirtenberg, and the Flossenburg subcamp at Freiberg. It is rumored that Hildegard Lachert also served at Mauthausen.

Several sub-camps of the KL Mauthausen included munitions factories, quarries, mines, arms factories and Me 262 assembly plants. Also, the inmates were used for slave labour at nearby farms. Those used at the quarries were working 12 hours a day until totally exhausted. Then the inmates were transferred to other concentration camps for extermination, or killed by lethal injection at the camp, and cremated in a local crematorium.

OSS officer LT Jack Taylor was captured and interned in Mauthausen. Several prisoners sacrificed thier lives so Lt. Taylor would be able to tell the Allies what had occured. Lt. Taylor was a key witness at the Dachau War Crimes Trials. Simon Wiesenthal was also interned in Mauthausen and liberated by the 11th Armored Division. Several American prisoners of war were also executed at Mauthausen.

The photo of the 11th Armored tanks arriving at Mauthausen (above) was actually taken on May 6, 1945 after S/SGT Kosiek and his squad had left the area and returned to an American camp site. LTC Seibel returned the next day (May 6) to take command of the concentration camp.