We studied spatial and temporal variation of Pb (lead), Cd (cadmium), and Cr+6 (chromium) in abiotic and biotic components of the Ganga River at Varanasi, which is situated in the river’s lower-middle stretch. River water, bottom sediment, and fish were collected seasonally at two sampling locations. Inductively coupled plasma emission spectroscopy (ICP-ES) was used for metal analysis. Cadmium and lead in the river water exceeded the permissible limit for drinking water prescribed by the World Health Organization. The geo-accumulation index (Igeo), contamination factor (CF), and ecological risk assessment (Er) revealed that Cd followed by Pb caused moderate to heavy contamination and posed potential ecological risk to the Ganga River system at Varanasi. The pollution load index (PLI) values were above “1,” indicating deterioration of sediment quality. Heavy metal concentration was determined in fish muscle tissues, and estimated daily intake (EDI) was calculated to evaluate potential health risk to consumer resulting from daily consumption of contaminated fish and the target hazard quotient (THQ). We also looked into the work of other researchers to observe temporal trend of heavy metals. Through this communication, we present a holistic status of metal contamination in the Ganga River system.