The area of what is now Kazo District was originally part of the chiefdom of Buhweju, which was incorporated into the Protectorate of Uganda in 1901 as part of the district of Ankole. After the 1971 Ugandan coup d'état, the district's name was changed to Mbarara. Kazo became part of Kiruhura District when it was split from Mbarara in 2005. In September 2015, Parliament approved the creation of Kazo District from Kiruhura, which went into effect on 1 July 2019.