Rivers play a crucial role in landscape evolution and human development, especially in arid zones, where hydrological resources are scarce and in high demand. The Atacama Desert is one of the world’s oldest and driest non-polar deserts, and aquatic systems therein have been historically subjected to anthropogenic pressure mainly associated with natural resource exploitation, such as water consumption for industrial mining activities. The mining industry has experienced a systematic development since the early 20th century, making Chile one of the main worldwide copper producers. This study analyzed sediments from two Atacama Desert rivers, the Loa and Salado Rivers (Antofagasta Region, Northern Chile). Sedimentary short-cores were obtained from sampled locations at varying distances from the confluence of the rivers. The characterization of chemical components, grain size, mineralogy, and magnetic properties of the rivers’ sediments was assessed in surface and subsurface samples to determine their respective signatures in the Inka-Coya Lake near the rivers’ confluence. The magnetic mineralogy present in the sediments of both rivers is composed of detrital magnetite and maghemite interspersed with those of authigenic origin. However, the downstream Loa River concentrated more authigenic minerals than the Salado and increased the abundance of silt-sized particles. The grain size of the Loa’s channel bed suggests low stream competency and high formation of depositional habitats. The magnetic signal and mineralogical composition of sediments from the lake are dominated by detrital pyrite, magnetite, and authigenic greigite. In contrast, the river’s sediments were dominated by magnetite and maghemite of detrital origin intercalated with those of authigenic origin. The granulometry, mineralogy, and rock magnetic properties of Inka-Coya Lake sediments indicate recent detrital input alternating with authigenic mineral-rich layers, mainly reflecting shifts in hydrological regimes. The highest concentrations of copper were observed in the upper, more recent sediment layers. Future scenarios of risky climatic conditions associated with increasing global metal demands could modify the availability of potentially toxic elements and transport capability in fluvial sediments, increasing the threats to water resource conservation in the world’s most arid desert.