The health risk caused by metal pollution is a global concern due to potential metal bioaccumulation, toxicity, and carcinogenicity with multiple sources and pathways. Here, the factors influencing metal bioaccumulation in more than a thousand fish individuals were investigated along a 5464 km continuum of the heavily sediment-laden Yellow River and the health risks to humans were evaluated. The average concentrations of Cr, Zn, As, Cu, Cd, and Pb were below the permissible limits established by domestic and foreign organizations. The fish showed biomagnification of Se and Sn through trophic transfer and a growth dilution effect for V, Mn, Co, Ni, Cu, Zn, As, Cd, and Ba. The concentrations and distributions of most metals in fish were mainly influenced by the trophic levels (δ15N) of fish and the content of the metals in the aquatic environment. The consumption of fish from the Yellow River does not pose a noncarcinogenic risk to the health of adults and juveniles. Cr and As could cause carcinogenic risks, and Cd and Pb also have carcinogenic risks, but these were within an acceptable range. The carcinogenic risks of fish consumption were relatively low in regions with low levels of metal pollution, such as the source region, while the risks were high in regions with heavy pollution and carnivorous fish at high trophic levels. In response to this threat, people can minimize these risks by adjusting their diet and appropriately reducing their consumption of aquatic products from the Yellow River.