Land use and land cover (LULC) change has become a matter of great concern in Kamonyi District due to increasing population, agricultural activities, and rapid settlement expansion. The current study evaluated the effect of anthropogenic activities on LULC change using a mixed methodology research design comprising remote sensing and a socioeconomic survey. The study involved 100 households selected through appropriate sampling procedures, as well as purposively selected key informants comprising 5 local leaders, 8 land management officers, and 1 District Environmental Officer. The combination of geospatial analysis and socioeconomic information enabled the study to comprehensively assess the patterns, drivers, and effects of human activities on LULC change. Image processing revealed that the percentage of built-up cover increased from 4% to 18%, while forest and natural vegetation decreased between 2015 and 2025. Moreover, croplands remained the dominant land cover. Population pressure (4.36 ± 0.78) and settlement development (4.28 ± 0.83) were the leading anthropogenic activities that triggered LULC change in the study area. Pearson correlation and multiple regression analysis showed a positive relationship between human activities and land cover change. In particular, the study found that settlement development (r = 0.91) and population pressure (r = 0.88) had the greatest impact on LULC change. The study also found that 92% of the variations in built-up and 89% of the variation in vegetation changes were explained by the model. The study recommends sustainable land-use planning and regulation of settlements to promote environmental management in Kamonyi District.