Wetlands are essential for protein production, water sanctification, groundwater recharge, climate purification, nutrient cycling, decreasing floods and biodiversity preservation. The Mursidabad district in West Bengal (India) is situated in the floodplain of the Ganga–Padma and Bhagirathi rivers. The region is characterized by diverse types of wetlands; however, the wetlands are getting depredated day-by-day due to hydro-ecological changes, uncontrolled human activities and rapid urbanization. This study attempted to explore the health status of the wetland ecosystem in 2013 and 2020 at the block level in the Mursidabad district, using the pressure–state–response model. Based on wetland ecosystem health values, we categorized the health conditions and identified the blocks where the health conditions are poor. A total of seven Landsat ETM+ spaceborne satellite images in 2001, 2013 and 2020 were selected as the data sources. The statistical data included the population density and urbanization increase rate, for all administrative units, and were collected from the census data of India for 2001 and 2011. We picked nine ecosystem indicators for the incorporated assessment of wetland ecosystem health. The indicators were selected considering every block in the Mursidabad district and for the computation of the wetland ecosystem health index by using the analytical hierarchy processes method. This study determined that 26.92% of the blocks fell under the sick category in 2013, but increased to 30.77% in 2020, while the percentage of blocks in the very healthy category has decreased markedly from 11.54% to 3.85%. These blocks were affected by higher human pressure, such as population density, urbanization growth rate and road density, which resulted in the degradation of wetland health. The scientific protection and restoration techniques of these wetlands should be emphasized in these areas.