During World War II, Nazi Germany occupied Netherlands from 1940 to 1945. In 1942, the Nazis transported Jewish and other prisoners from the Netherlands via the transit camps Amersfoort and Westerbork to the Auschwitz concentration camp, except for 850 prisoners sent to Mauthausen concentration camp. When Amersfoort and Westerbork proved to be too small to handle the large number of prisoners, the Schutzstaffel (SS) decided to build a concentration camp in Vught, near the town of 's-Hertogenbosch.

The building of the camp at Herzogenbusch, the German name for 's-Hertogenbosch, started in 1942. The camp was modelled on concentration camps in Germany. The first prisoners, who arrived in 1943, had to finish the construction of the camp, which was in use from January 1943 until September 1944. During that period, it held nearly 31,000 prisoners: Jews, political prisoners, resistance fighters, Gypsies, Jehovah’s Witnesses, homosexuals, homeless people, black market traders, criminals, and hostages.

Due to hunger, sickness, and abuse, at least 749 men, women and children died in Herzogenbusch. Of those, 329 were murdered at the execution site just outside the camp. As allied forces approached Herzogenbusch, the camp was evacuated and the prisoners were transferred to concentration camps further east. By 4–5 September 1944, the women inmates had been sent to Ravensbrück Concentration Camp, and the men to Sachsenhausen concentration camp . On 26 October 1944, Scottish troops of the 7th Black Watch, and Canadian troops of the 4th Canadian Armoured Division's 96th Battery, 5th Anti-tank Regiment, liberated the camp after fighting a rear guard of SS personnel left to defend the nearly evacuated facility. There were around 500-600 prisoners left alive, who were due to be executed that afternoon, and whose lives were saved by the arrival of the liberating forces. About 500 inmates were also discovered dead in piles near the gates, having been executed the very morning of the day the camp was liberated.

In the first years following the war, the camp was used for the detention of Germans, Dutch SS men, alleged collaborators and their children, and war criminals. At first, they were guarded by allied soldiers, but shortly after by the Dutch.