Characterized by a predominantly agricultural landscape, including rice paddy, agricultural land, and scattered forest, the Chrey Bak catchment of the Tonle Sap Lake, Cambodia, is experiencing challenges such as deforestation and land conversion, which negatively impact mineral alteration sources, land management, and ecosystems. The current study uses satellite data (Sentinel 2, Landsat-8 OLI, and ASTER) to detect changes in mineral alteration (i.e., iron oxide and clay) and in land use and land cover (LULC) and to examine their relationships with the catchment’s lithology. Sentinel-2 satellite imagery between 2015 and 2022 was used to classify LULC changes. The visible and near-infrared (VNIR) and the short-wave infrared (SWIR) bands were used to map the iron oxide and clay deposits, thereby reducing the time and cost associated with fieldwork. The results revealed significant LULC changes, with a decrease in vegetated areas and an increase in cropland and built-up areas, while remaining unchanged for forested areas and water bodies. These changes have direct implications for mineral alteration, as the areas with land conversion (i.e., agricultural areas) showed their exposure to mineral-rich areas, particularly those containing iron oxide and clay. This study contributes to a qualitative understanding of the relationships between LULC changes across litho-mineral substrates, offering insights that can inform sustainable land management practices and mineral exploration efforts in the catchment.