Disease resistance of inbred and novel intra-specific crossbred fingerlings of Clarias gariepinus (Burchell, 1822) in response to Aeromonas hydrophila challenge was assessed in fisheries and aquaculture research farms with the goal of assessing symptoms, survival and growth rate in fingerlings of novel inbred and crossbred genotypes of C gariepinus, in order to explore their potentials for improved aquaculture. The result demonstrates that survival and growth rates differed significantly across genotypes control and challenged treatments. Fish from challenging treatments exhibited darker coloration, slower swimming, swelling of the lower belly, ulceration, and death. 10% of the challenged ♀Bn x ♂Bn and ♀Dg x ♂Bn perished within 72 hours, while all control treatments survived. At two week, the survival rates of the challenged ranged from 30% in ♀Bn x ♂Dg, 40% in ♀Dg x ♂Dg, 80% in both ♀Bn x ♂Bn and ♀Dg x ♂Bn. Except for ♀Dg x ♂Bn, ♀Bn x ♂Dg, ♀Bn x ♂Bn and ♀Dg x ♂Bn: 2.21±0.06d, 0.98±0.1c and 0.1±0.1ab, growth rate were considerably greater in challenged than in control. C. gariepinus crossbreed (♀Dg x ♂Bn) tolerated A. hydrophila infection better than crossbreed (♀Bn x ♂Dg). The crossbreed C. gariepinus (♀Dg x ♂Bn) will increase fish production and profitability under illness challenges. If several selective breeding and back crossing of the strains and one of the parents are conducted between rivers Benue and Donga, there is possibility of obtaining fish seed with improved reproductive potential in terms of survival, growth, mortality rate, and disease resistance in terms of A. hydrophila challenge.