The study evaluated the acute toxicity of vehicle wastewater on African catfish (Clarias gariepinus). With a weight range of 250–275.5g and a mean length of 23.5-28.5cm, 150 post-juvenile catfish were purchased from Dalar Kifi Fish Farm BUK New site road, Kano State, and acclimated in a tank for 14 days. Fish were exposed to different vehicle wastewater concentrations of 0.0, 20, 40, 60, and 80% v/v with 5-level exposure concentrations during the acute test (96 hours) in a Completely Randomized Design (CRD) employing renewal bioassay. The acute bioassay showed that the LC50 for the wastewater was 56 percent by volume at 96 hours. Compared to the control, the exposed fish exhibited abnormal swimming, erratic opercular movement, reflex loss, mucus secretion, increased air gulping with an increase in wastewater concentration. Except for water temperature, Biochemical Oxygen Demand (BOD) and pH, the remaining physicochemical parameters were not within the WHO/FAO recommended Standard The order of concentrations of the heavy metal in the wastewater was Cu > Pb > Cd > Cr > Ni. Antioxidant biomarker activities showed that Glutathione reductase (GSH) reduced in the same manner while Catalase (CAT) and Superoxide dismutase (SOD) activities rose considerably (P<0.05) in the liver and gill tissues. Histopathological changes observed in gill tissues were as follows: Hyperplasia, necrosis, primary and secondary lamellae distortion, and epithelial thickening distortion. Hepatic cell breakdown, fatty degeneration, cellular infiltration, localized fibrosis, and cellular necrosis were all visible in the liver tissues. It can be inferred that changes in the histology and activity of the oxidative stress enzymes in fish tissues after exposure to wastewater harmed the experimental fish. As a result of their effects on fish and other non-target aquatic biotas, it is advised that the competent authorities create initiatives to reduce the indiscriminate discharge of untreated vehicle wash wastewater.