The bioaccumulation of heavy metals (HMs) in marine fish is a growing global concern due to potential human health risks. The study analyzed HM in the muscle tissue, gills, and gut of adult male and female cape horse mackerel and slinger seabream caught in the polluted Durban Basin and pristine Cape Vidal from April 2018 to February 2019. Results revealed interspecific, spatial, and organ-specific variability in HM levels. In the Durban Basin, slinger seabream had bioaccumulation (in mg/kg) of As (2.3 ± 0.2), Cr (2.6 ± 0.2), Ni (2.0 ± 0.1), and Pb (4.1 ± 0.3) while cape horse mackerel had Ni (1.6 ± 0.2), Pb (4.7 ± 0.6), and Zn (52 ± 3.01) exceeding World Health Organization (WHO) regulatory limits. Metal pollution index (MPI) values were also higher in Durban Basin (> 5.13) than Cape Vidal (< 3.32) for both species’ muscles. Liver and gills of slinger seabream and gut of cape horse mackerel exhibited higher HM accumulation patterns proportionate to the environmental concentrations, indicating the bioindicative potential of HM pollution by the two species. Risk assessment indicated that both fish species had target hazard quotient > 1 for Cr, and target cancer risk < 10–4 for Pb, implying significant potential non-carcinogenic and carcinogenic health risks associated with fish consumption from the Durban Basin. The study recommends daily consumption limits of 16 g/day for slinger seabream and 14 g/day for cape horse mackerel to ensure health safety. The findings contribute to the understanding of HM pollution in the Durban Basin and provide important information for decision-makers and policymakers in developing effective strategies to mitigate and manage HM contamination in fish populations.