The current study was conducted to assess hemato-biochemical and genotoxic changes caused by Grass carp’s exposure to toxic heavy metals. The fish C. idella was exposed to sub-lethal concentrations (1/20th of 96-h LC50) of cadmium (5.7 mg/l), lead (7.6 mg/l), and mercury (0.6 mg/l), for one week. The blood measurements of the treated groups demonstrated a significant decrease (p < 0.05) in the levels of RBCs, hemoglobin, MCHC, WBCs, lymphocytes, and platelets, whereas there was a significant increase (p < 0.05) in the MCH and MCV values. The analysis of blood biochemistry unveiled a significant increase (p < 0.05) in metabolites (such as cholesterol, glucose, creatinine, and urea) and electrolytes (potassium and sodium). Conversely, the levels of triglycerides, serum proteins, calcium, and phosphorus exhibited a significant decline (p < 0.05) in comparison to the untreated group. The percentage for DNA damage for erythrocytic cells was noted for the exposed concentrations of Cd, Pb, and Hg with a significant increasing pattern (p < 0.05) following the sequence Pb > Hg > Cd. The results demonstrated that the Comet test is precise for determining toxicity and can be applied in environmental monitoring activities. This study concluded that excessive use of these heavy metals can negatively affect the health of fish.