The Order of Saint Benedict decided in 1905 to establish a mission in the Kimberley's far north. Three years later, Benedictine monks from New Norcia founded it at Pago, near the southern end of Napier Broome Bay, about twenty kilometres from the current site. Water supply problems plagued the early settlement for decades. In 1937 — the same year the mission ship Koolama was being built in Glasgow — the missionaries finally moved to their current location at Kalumburu Pool, on the King Edward River. The community they established, known until 1951 as Drysdale River Mission, was and remains a long way from the institutional centres of the Church. Benedictine nuns and a priest continue to maintain a presence there today, part of a community that is now majority Catholic and almost entirely Aboriginal.

When World War II reached the Pacific, Kalumburu was transformed almost overnight. The Australian government commissioned an airfield at the mission, and after Japanese forces occupied the Dutch East Indies in 1942, Drysdale River became a frontline Royal Australian Air Force base. Allied squadrons used it as a staging post, and RAAF anti-submarine aircraft refuelled and rearmed there on routes between Darwin and Fremantle. On 20 February 1942 — the day after the first Japanese bombing of Darwin — the mission ship Koolama was attacked by Japanese aircraft nearby and beached; the mission at Drysdale River sent a lugger and assisted survivors beginning around 25 February. On 2 December 1942, eight Beaufighters from No. 31 Squadron RAAF launched from Drysdale River in a pre-emptive strike on Japanese aircraft at Penfui near Kupang, destroying eighteen planes on the ground. The war had arrived at the end of the most remote road in Western Australia.

On 27 September 1943, twenty-one Japanese Kawasaki Ki-48 bombers flew from Kupang, Timor, with a fighter escort and attacked the base and settlement. Father Thomas Gil, the mission's superior, aged 45, was killed. Five Aboriginal residents died alongside him, ranging in age from one year old to 45 — including a mother and her son. The community buried them together in the mission grounds, the Aboriginal people on either side of Father Thomas, following a funeral held in the damaged church. The image is one of the more striking of the war's reaches into remote Australia: a Spanish Benedictine monk and five Aboriginal Australians, killed by Japanese bombers three thousand kilometres from any front line, buried together in the red dirt of the Kimberley. The airfield's importance eventually declined after Truscott Airfield was constructed about 32 kilometres to the north in 1944.

Kalumburu was officially renamed from Drysdale River Mission in 1951. Management of the community has since passed to the Kalumburu Aboriginal Corporation on behalf of the Kalumburu Community Council. The remoteness that defined the settlement in 1908 has not substantially diminished: the nearest hospital remains 568 kilometres away over a poor-quality road — a twelve-hour journey in the dry season. Two remote area nurses staff the community clinic, with a visiting doctor arriving once a week. The Royal Flying Doctor Service uses the Kalumburu airstrip, and the old Truscott Airbase can serve emergencies. The population of around 388 (as of the 2021 census) is 88.4 percent Aboriginal and Torres Strait Islander. The community retains its Catholic character and its Benedictine connections, carrying forward a history layered with colonialism, faith, war, and an enduring Aboriginal presence that predates all of it.