The university has two campuses. The main campus is located in the city of Masaka, approximately 145 kilometres (90 mi), by road, southwest of Kampala. The second campus is located on Mengo Hill, the seat of the Buganda Government, within the city of Kampala.
The University was established when ownership of Masaka Technical Institute (Uganda Technical College, Masaka), was transferred from the Government of Uganda to the Buganda Government, in January 2007. The University is named after Kabaka Muteesa I Mukaabya Walugembe Kayiira. He made agreements with the British to introduce British-based education in his kingdom (Buganda) in the late 19th century. Muteesa I Royal University received Tertiary Education Institution accreditation from the Ministry of Education & Sports in July 2007. The university admitted the first class of students in October 2007. The university will hold its first graduation ceremony on Friday 15 April 2011. At the same ceremony, His Majesty Ronald Edward Frederick Kimera Muwenda Mutebi II will be installed as the first Chancellor of the university.