Background: The burden of Kaposi sarcoma (KS) is increasing fast among HIV-infected populations, but the disease remains desperately underexplored in Cameroon, where the burden of HIV is high. Methods: This is a retrospective cross-sectional study carried out over a period of 16 years (January 2001 to December 2016) at the HIV day care unit of the Central Hospital of Yaoundé, Cameroon. The diagnosis was based on clinical aspects and histological confirmation, and we used a preconstructed questionnaire for data collection through patients’ electronic and physical files. Results: Among 14,220 files reviewed, 316 cases of KS were identified, yielding a cumulative incidence of 2.2%. In the end, 266 patients (55% male) were included in this study. The patients’ age ranged from 17 to 72 years, with a mean of 37.8 ± 9.5 years. KS was the presenting manifestation of HIV in 89.8% of the cases. Cutaneous lesions occurred more often (81.6%), mainly located on the lower limbs (47.7%); mucous lesions were found in 15.8% of the patients, while 8 patients (3.0%) had associated visceral lesions. The lesions predominantly were lymphedemas (28.6%) and papulonodules (21.1%). At the diagnosis of KS, the median CD4 count was 175 cells/mm3 (interquartile range 80.5–288.5), and 150 patients (56.6%) had CD4 counts < 200 cells/mm3. Conclusions: KS is frequent among our HIV-infected patients; it seems to occur most often at a younger adult age and represents one of the presenting manifestations of HIV/AIDS in our context. It seems to equally affect men and women, occurring more often when CD4 counts are < 200 cells/mm3.