Levels of organochlorine (OC) and organophosphorus (OP) pesticide residues in fish, sediments and water and their health risk associated with the consumption of the fish from the Tono Reservoir, Ghana were evaluated. The analytical methods included solvent extraction of the pesticide residues using ultrasound sonication and soxhlet extraction and their subsequent quantification using GC equipped with electron capture detector and pulse flame photometric detector after clean-up on activated silica gel/anhydrous sodium sulphate. A total of 29 pesticides comprising 16 OCs and 13 OPs were analyzed, out of which aldrin, p,p′-DDE and p,p′-DDD were detected in fish and sediment samples. The results showed that all the residues in water had their concentrations below the detection limit. Mean concentrations of organochlorine pesticide (OCP) residues in fish ranged from 0.017 to 0.17, 0.043 to 0.30, 0.027 to 0.243 and 0.097 to 0.263 µg/g in Sarotherodon galilaeus, Clarias anguillaris, Schilbe intermedius and Marcusenius senegalensis respectively. Mean concentrations of organophosphates pesticides ranged from 0.080 to 0.090, 0.080 to 0.087 and 0.050 to 0.063 µg/g in C. anguillaris, S. intermedius and M. senegalensis respectively. The level of chlorpyrifos in S. galilaeus was 0.160 µg/g. Mean concentrations of OCP residue in sediments ranged from 0.047 to 0.090 µg/g. Aldrin recorded the highest level while p,p′-DDD recorded the lowest level. The mean concentrations for all the detected residues were below the WHO/FAO maximum residue limits. Health risk estimation revealed that aldrin in M. senegalensis had great potential for systemic toxicity to consumers.