The herbicide, 2,4-D is commonly used to control broad leaf weeds in agriculture and to eliminate aquatic weeds. Run-offs to floodplains that serve as breeding sites of some fish species such as Clarias gariepinus is common. This study was undertaken to evaluate the effects of 2,4-D on the behaviour, haematology and histology of the African catfish, C. gariepinus, in order to understand its toxicity. Juvenile catfish weighing 10.03±14.1g were exposed to lethal concentrations and subsequently three sublethal concentrations (0.43, 0.58 and 0.72mg/L) of 2,4-D. The behaviour of the fish was observed during exposure and after 96h, the blood and tissues from the liver, kidney, fin, brain and gills were collected and analyzed. The result showed that exposed fish displayed signs of asphyxiation. The packed cell volume (PCV), red blood cell (RBC) and haemoglobin (Hb) significantly decreased by 17-40% while white blood cell (WBC) increased significantly (p<0.05) by 78-137% in a concentration dependent pattern. Histopathological analysis showed extensive damage to the liver, kidney, fin, brain and gills of the fish exposed to sublethal concentration, which suggests that 2,4-D causes deleterious harm to hepatocytes and renal, neural, fin and gill cells. Damage to the gill filaments could impair oxygen uptake resulting in asphyxia and consequently death over a period. The study clearly shows that C. gariepinus is highly susceptible to the toxicity of 2,4-D, therefore the use of this herbicide in rice paddies near the breeding sites of the fish should be discouraged.