Pesticides from agricultural run-off pose a severe threat to non-target organisms, such as fishes. This study was carried out to evaluate acute toxicity and histological and genotoxic effects (erythrocytic nuclear abnormalities) of lethal and sublethal concentrations of three commonly used pesticides: Atrazine, Butachlor and Glyphosate on the African mud catfish (Clarias gariepinus). Fishes were exposed to the pesticides for 96h periods to determine their LC 50 and the sub-lethal effect at various concentrations (1/10th, 1/100th, 1/1000th 96h LC50) over 28 days. The 96h LC 50 values were 7.63mg/l, 0.7mg/l and 15.97mg/l for atrazine, butachlor and glyphosate, respectively. Histological sections of the liver of C. gariepinus exposed to the three pesticides showed mild vascular congestion but no necrosis in the tissue. There was a significant (p<0.5) dose-dependent increase in micronuclei and nuclear abnormalities in the erythrocytes of exposed C. gariepinus compared to the control by 28 days. The study confirmed that C. gariepinus are at risk of adverse effects from exposure to pesticides. Discharge of agricultural run-off around water bodies should be prevented or prohibited to avoid adverse effects on aquatic life.