This study is the first in forming an integrated up-to-date spatial analysis linking heavy metal contamination among three different compartments of Lake Edku ecosystem to human health effects. The study determined the concentrations of iron (Fe), nickel (Ni), lead (Pb), chromium (Cr), and cadmium (Cd) in sediment and water samples collected from 12 stations covering the entire lake, as well as in the liver and muscle tissues of the three commercially edible fish species (African sharptooth catfish (Clarias gariepinus), Blue tilapia (Oreochromis aureus), and Redbelly tilapia (Tilapia zillii)), during winter 2019. Cartographic maps investigating the spatial contamination pattern of each metal in sediment and water samples along the entire lake, as well as correlation analysis between metal pairs, were generated. Moreover, the study examined the affinity of metal transfer among the three compartments and assessed the probability of being exposed to non-carcinogenic health hazards from the consumption of the abovementioned species. Results revealed that Fe and Cd recorded the highest and lowest mean concentrations, respectively, in sediment, water, and fish samples. The mean concentrations of Cd, Pb, and Ni in the water of Lake Edku, as well as the mean concentrations of Cd, Pb, and Cr in muscle tissues of the three examined fish species, exceeded the permissible limits. The northwestern part of the lake exhibited the highest concentrations of Fe, Ni, and Cr in Lake Edku's sediment with strong significant positive correlations recorded between Fe-Ni, Fe-Cr, and Ni-Cr pairs suggesting sharing the same contamination source. Concerning Lake Edku's water, the northwestern area displayed the highest concentrations for all metals. Moreover, Cd, Pb, and Cr exhibited nearly the same spatial contamination pattern with the hotspot located in the western part of the lake. Strong significant positive correlations were found between Cd-Pb, Cd-Cr, and Pb-Cr pairs in surface water, suggesting sharing the same origin of dispersion. The three fish species accumulated heavy metals from water several folds higher than from sediments, indicating that water is the main source of the intensive transfer of heavy metals to the three fish species. Based on the consumption of the three investigated fish species, children recorded the highest estimated daily (EDI) and weekly intakes (EWI) of heavy metals followed by adults. Regardless Pb, EWI values indicated that there are no significant health risks through fish consumption from the examined metals recommending that children should consume less than 85.227 g/day African sharptooth catfish muscle, 108.696 g/day Blue tilapia muscle, and 97.403 g/day Redbelly tilapia muscle to assure their health. Moreover, adults should consume less than 397.727 g/day African sharptooth catfish muscle, 507.24 g/day Blue tilapia muscle, and 454.54 g/day Redbelly tilapia muscle. The estimated hazard quotient (HQ) of all metals was lower than or close to the safe values of one for children and adults in the three investigated fish species indicating the absence of potential non-carcinogenic threats. The hazard index (HI) estimated for the five examined heavy metals in each of the investigated fish species was below one in adults only. Regarding the total hazard index estimated from consuming the three fish species, both children and adults may be subjected to non-carcinogenic risk.