Ntoroko District is one of the two Ugandan districts west of the Rwenzori Mountains, the other being Bundibugyo District. The Ntoroko District is bordered by the Democratic Republic of the Congo to the west and north, Hoima District to the north-east, Kibaale District to the east, Kabarole District to the south, and Bundibugyo District to the south-west. The town of Ntoroko is approximately 144 kilometres (89 mi), by road, north-east of Kasese, the largest town in the Rwenzururu sub-region. This location is approximately 376 kilometres (234 mi), by road, west of Kampala, the capital and largest city of Uganda.

The Ntoroko District was created by the Ugandan Parliament and became operational on 1 July 2010. Before that, the district was part of the Bundibugyo District.

In 1991, the national population census estimated the district population at 24,300. The national census in 2002 estimated the population at 51,100. In 2014, the national census and household survey enumerated the district population at 67,005.