Fungal infections cause substantial morbidity and mortality. However, the burden of deep fungal infections is not well described in Uganda. We aimed to estimate the burden and etiology of histologically diagnosed deep fungal infections in Uganda. We retrospectively reviewed histology reports at the Pathology Reference Laboratory, Department of Pathology, Makerere University, Kampala, Uganda from January 1950 to September 2019 to identify any reports that had a fungal infection as the diagnosis. Over the study period, 697 cases of deep fungal infections were identified with an average incidence of 0.73/100,000 persons per decade. There was a general decline in the number of cases detected. Median age of the cases was 28 years (IQR: 11-40) and majority (59%) were male. The age group of 0-10 years were the most affected. The foot was the most affected part of the body (26%). Deep mycoses identified include eumycetoma (32%), subcutaneous phycomycosis (26%), histoplasmosis (9.2%), chromoblastomycosis (4.6%), aspergillosis (3.3%), cryptococcosis (3.3%), blastomycosis (1.6%), subcutaneous mycosis (1.4%), dermatomycosis (1.3%), coccidioidomycosis (0.6%), mucormycosis (0.6%), and sporotrichosis (0.1%). Histoplasma was the commonest causative agent (9.2%) followed by Aspergillus (3.4%) and Cryptococcus (3.3%), while 81% of the fungal pathogens were not identified to genus/species level. Only 31% of the cases were diagnosed clinically as deep fungal infections. There is a substantial burden of deep fungal infections caused by multiple fungal pathogens in Uganda. There is need to build local capacity for mycology so as to improve on the index of clinical suspicion and diagnostic capabilities.