In order to assess the influencing factors of the presence of mercury in a river within the Savanna biome (Cerrado), we surveyed total mercury (THg) in bottom sediment from 50 lakes along 750 km of the Middle Araguaia floodplain. The sampling sites included non-urban and urban surroundings over three distinct geomorphologies. We measured water physicochemical parameters at each site and tested statistically if land use nested within the geological formation influenced the THg concentration in bottom sediments and related water parameters. Multivariate results indicate that the interaction between geological groups and land use is statistically significant (p p p p = 0.02). The spatial projections of the THg eigenvector on the main axes with the scoring factors of the Neoproterozoic/Paleoproterozoic terrains, and urban/non-urban, confirmed the spatial correlations. These results indicate that the association of land use and geology could be the main driver of THg in the bottom sediments of lakes from the Middle Araguaia floodplain.