Lead (Pb) is one of the toxins responsible for the deterioration of ecological health in aquatic environments. The present study investigated the effects of Pb(NO3)2 toxicity on growth, blood cell morphology, and the histopathology of gills, liver, and intestine of juvenile Nile tilapia, Oreochromis niloticus. A 30-day long aquarium trial was conducted by assigning three treatment groups T1 5.20 mg L−1, T2 10.40 mg L−1, and T3 20.80 mg L−1, and a control 0 mg L−1 following the 96 h LC50 of 51.96 mg L−1 from acute toxicity test. Overall growth performance significantly declined in all the Pb(NO3)2 treated groups and the highest mortality was recorded in T3. Behavioural abnormalities were intense in all the treatment groups compared to the control. Hepatosomatic index (HSI) values were reported as higher in treatment groups. Reduced nucleus diameter and nuclei size in erythrocytes were reported for T2 and T3 groups. Dose-dependent histological alterations were visible in the gills, liver, and intestine of all the Pb(NO3)2 treated groups. The width of the intestinal villi was highly extended in T3 showing signs of severe histological alterations. In conclusion, Pb toxicity causes a negative effect on growth performance, erythrocyte morphology, and affected the vital organs histomorphology of juvenile O. niloticus.