Background: Nephrotoxicity is common among cancer patients, yet some anti-cancer drugs, for example, platinum derivatives, are nephrotoxic and have narrow therapeutic indices. If nephrotoxicity is not managed, it can progress to kidney injury, which results in unregulated blood pressure, hormonal imbalance, electrolyte imbalance, body fluid imbalance and death. However, the burden of nephrotoxicity among adult cancer patients in Uganda is not documented in the literature. Objective: This study assessed the prevalence and risk factors of nephrotoxicity among cancer patients receiving chemotherapy at Mbarara Regional Referral Hospital Cancer Unit (MRRHCU). Methods: The study was a cross-sectional study carried out at the MRRHCU, Uganda. All the 206 adult cancer patients who received at least three cycles of chemotherapy and fulfilled the inclusion criteria were included. A data collection form was used to collect data, which was recorded into Microsoft Excel version 2013. Data were analyzed using Stata version 12.1. Results: Of the 206 participants, 74 (35.9%) developed nephrotoxicity with majority in stage 1 (n = 83, 40.3%) and stage 2 (n = 55, 26.7%). In the multivariate logistic regression of risk factors for nephrotoxicity, age >50 years old (aOR: 1.80, 95% CI: 1.06, 1.91; p > 0.001), hypertension (aOR: 1.71, 95% CI: 1.74, 1.94; p = 0.011) and use of platinum agents (aOR: 2.04, 95% CI: 1.82, 3.34; p = 0.002) were significant independent risk factors of nephrotoxicity. Conclusion: About one-third (1/3) of the adult cancer patients at MRRHCU develop nephrotoxicity, which indicates a high burden of nephrotoxicity. The prevention of progression of nephrotoxicity from grades 0, 1 or 2 to grade 3 or 4 is therefore necessary, especially among the patients with risk factors, such as hypertension and age >50 years old and use of platinum agents.