The Yamuna River and its wetlands in the Delhi National Capital Region (NCR) are globally significant due to their biodiversity. However, land use changes (LUC), population growth, and pollution pose threats to these ecosystems. This study employed remote sensing (RS) and geographic information system (GIS) methods using Landsat satellite data from 1998 to 2018 to evaluate anthropogenic changes along a 22 km stretch of the river. This study focused on assessing LUC in the Yamuna River corridor from Wazirabad Barrage to Okhla Barrage. Land use land cover (LULC) maps derived from satellite data were utilized to analyze changes in the river's size and surrounding land use. The results reveal a substantial increase in built-up areas along the river, with a growth of 1.92% between 1998 and 2008 and 8.91% between 2008 and 2018. Cropland/agricultural land expanded by 3.96% between 1998 and 2008 but experienced a slight decline of -5.34% during 2008 to 2018. The forest land showed a reduction from 111.33 km2 (10.13%) in 1998 to 74.90 km2 (6.82%) in 2008, with a modest growth of 76.48 km2 (6.96%) identified in 2018. The study highlights an alarming rate of deforestation, as reflected by the negative dynamic index of the forest land. Water bodies exhibited a consistent negative trend over the research period, while the area covered by barren land expanded. This study underscores significant LUC along the Yamuna River from 1998 to 2018, characterized by increased built-up areas and reduced forest cover. The decline in water bodies and expansion of barren land further emphasize the need for monitoring LUC and its impact on the river and its wetlands. The findings provide valuable insights for policymakers to develop strategies aimed at protecting the region's biodiversity and mitigating threats facing the Yamuna River and its wetlands.