The issue of mercury (Hg) is becoming a growing concern in the Amazon basin. The Madeira River is known for intense artisanal and small-scale gold mining (ASGM), and Hg poses a significant issue for public health and ecosystems. In this study, we analyzed Hg riverine concentrations in water samples, suspended particulate matter (SPM) and sediments in the Upper Madeira River Basin. We also examined mineralogical and elemental compositions of the solid phase to enhance our understanding of Hg behavior in the environment. Dissolved Hg was not detected in water, and Hg concentrations in solids remained in the same order of magnitude across different rivers, despite variations in gold mining intensities along their courses. Generally, Hg concentrations were higher in compartments with a greater proportion of fine sediments (clay and silt), with average concentrations of 91.4 ± 13.0, 41.6 ± 11.0, and 22.2 ± 1.6 ng g−1 for SPM (n = 14), riverbank (n = 12), and riverbed (n = 4) sediments, respectively. Multivariate analysis shows Hg chemical associations related to clay minerals and organic matter (OM) for the riverbank and SPM compartments. However, in SPM, OM had a greater influence on Hg distribution. Conversely, one riverbed sample highlights with a high Hg concentration (547.78 ng g−1), large content of heavy minerals, and a distinct geochemical signature. This sample was collected in a river section upstream of Beni River's rapids where the river's hydrodynamics can induce the high concentration of heavy minerals in this riverbed sediment. This unexpectedly high Hg concentration encountered in sediment rich in heavy minerals is likely related to contamination by Hg-rich mine tailing discarded into the river. Overall, this study discusses the issue of Hg mobility in rivers suggesting its dispersion, i) associated with fine fraction rich in clay and OM, and ii) associated with heavy minerals.