The Indian Sundarbans, together with Bangladesh, comprise the largest mangrove forest in the world. Reclamation of the mangroves in this region ceased in the 1930s. However, they are still subject to adverse environmental influences, such as sediment starvation due to migration of the main river channels in the Ganges–Brahmaputra delta over the last few centuries, cyclone landfall, wave action from the Bay of Bengal—changing hydrology due to upstream water diversion—and the pervasive effects of relative sea-level rise. This study builds on earlier work to assess changes from 2000 to 2020 in mangrove extent, genus composition, and mangrove ‘health’ indicators, using various vegetation indices derived from Landsat and MODIS satellite imagery by performing maximum likelihood supervised classification. We show that about 110 km2 of mangroves disappeared within the reserve forest due to erosion, and 81 km2 were gained within the inhabited part of Sundarbans Biosphere Reserve (SBR) through plantation and regeneration. The gains are all outside the contiguous mangroves. However, they partially compensate for the losses of the contiguous mangroves in terms of carbon. Genus composition, analyzed by amalgamating data from published literature and ground-truthing surveys, shows change towards more salt-tolerant genus accompanied by a reduction in the prevalence of freshwater-loving Heiritiera, Nypa, and Sonneratia assemblages. Health indicators, such as the enhanced vegetation index (EVI) and normalized differential vegetation index (NDVI), show a monotonic trend of deterioration over the last two decades, which is more pronounced in the sea-facing parts of the mangrove forests. An increase in salinity, a temperature rise, and rainfall reduction in the pre-monsoon and the post-monsoon periods appear to have led to such degradation. Collectively, these results show a decline in mangrove area and health, which poses an existential threat to the Indian Sundarbans in the long term, especially under scenarios of climate change and sea-level rise. Given its unique values, the policy process should acknowledge and address these threats.