Spatial distribution and pollution assessment of selected heavy metals such as barium (Ba), chromium (Cr), nickel (Ni), lead (Pb), vanadium (V), arsenic (As), zinc (Zn), and copper (Cu) in sediments of the Brahmaputra River watershed in Bangladesh was investigated. The mean abundances (ppm) of heavy metals in sediment samples were in decreasing order Ba (375.60) > V (67.60) > Cr (54.10) > Zn (48.20) > Ni (22.28) > Pb (20.25) > Cu (7.59) > As (4.21). Concentrations of Pb and As in the sediments are enriched relative to the average upper continental crust composition, while Ba, V, Cr, Zn, Ni, and Cu decrease considerably. A higher concentration of Pb and Ni indicates that Brahmaputra River watershed samples receive a significant contribution from anthropogenic sources of heavy metals. Chromium displays marked positive correlation with V (r = 0.91, p =  < 0.01), inferring a similar source materials input into the watershed. The geo-accumulation index (I) values suggest that the sediments were uncontaminated to moderately contaminated by Ni, Zn, Pb, V, and Cr, whereas moderate to heavily contaminated by As and Cu. The contamination factor (CF) confirmed that sediments in the watershed were moderate to highly contaminated by As, Cu, and Cr. The pollution load index (PLI) values for most of the samples were over one (> 1), indicating an advanced decline in the watershed sediment quality. The overall results of a multivariate statistical analysis suggest that Ba, V, Cr, and Zn contents were all-natural sources, and Pb, Ni, As, and Cu were derived from both natural and anthropogenic sources.