The Karnaphuli, a major river of Bangladesh, located off the coast of Chittagong in the Bay of Bengal is largely exposed to the heavy metal pollutants, which may be toxic to humans and aquatic fauna. The estuary is a striking example of a site where human pressure and ecological values collide with each other. In spite of being a major supplier of fish food for local community, there has been no study carried out to date to assess the potential human health risk due to heavy metal contamination in the fish species from this estuary. Therefore, the aim of present study was to assess bioaccumulation status and the potential human health risk evaluation for local consumers. Six commercially important fish species, Apocryptes bato, Pampus chinensis, Hyporhamphus limbatus, Liza parsia, Mugil cephalus, and Tenualosa toil from the Karnaphuli River estuary were collected to analyze heavy metals concentration level. Heavy metals As, Pb, Cd, Cr and Cu were detected from the samples using inductively coupled plasma mass spectrometry (Model: ELAN9000, Perkin-Elmer, Germany). The hierarchy of the measured concentration level of the metals was as follows: Pb (mean: 13.88, range: 3.19 - 6.19) > Cu (mean: 12.10, range: 10.27 - 16.41) > As (mean: 4.89, range: 3.19 – 6.19) > Cr (mean: 3.36, range: 2.46 – 4.17) > Cd (mean: 0.39, range: 0.21 - 0.74). The Fulton’s condition factor denoted that organisms were particularly in better ‘condition’ and most of the species were in positive allometric growth. The Bioaccumulation factors (BAFs) observed in the species of the contaminants were organized in the following ranks: Cu (1971.42) > As (1042.93) > Pb (913.66) > Cr (864.99) > Cd (252.03), and among all the specimens, demersal fish, A. bato corresponded to the maximum bio-accumulative organism. Estimated daily intake (EDI), target hazard quotient (THQ) and carcinogenic risk (CR) assessed for human health risk implications suggest that the values are within the acceptable threshold for all sorts of consumers. Hence none of them would experience non-carcinogenic and carcinogenic health effect for the ingestion of the fishes. However, children are shown to be largely susceptible than adults to non-carcinogenic and carcinogenic health effect due to the consumption of fish. Therefore, an appropriate guidlines and robust management measures needed to be taken to restore the estuarine health condition for greater benefit of the quality of fish products for local consumption.Graphical abstract