Globally, mangrove forests are substantially declining, and a globally synthesized database containing the drivers of deforestation and drivers’ interactions is scarce. Here, we synthesized the key social-ecological drivers of global mangrove deforestation by reviewing about two hundred published scientific studies over the last four decades (from 1980 to 2021). Our focus was on both natural and anthropogenic drivers with their gradual and abrupt impacts and on their geographic coverage of effects, and how these drivers interact. We also summarized the patterns of global mangrove coverage decline between 1990 and 2020 and identified the threatened mangrove species. Our consolidated studies reported an 8600 km2 decline in the global mangrove coverage between 1990 and 2020, with the highest decline occurring in South and Southeast Asia (3870 km2). We could identify 11 threatened mangrove species, two of which are critically endangered (Sonneratia griffithii and Bruguiera hainseii). Our reviewed studies pointed to aquaculture and agriculture as the predominant driver of global mangrove deforestation though their impacts varied across global regions. Gradual climate variations, i.e., sea-level rise, long-term precipitation, and temperature changes and driven coastline erosion, salinity intrusion and acidity at coasts, constitute the second major group of drivers. Our findings underline a strong interaction across natural and anthropogenic drivers, with the strongest interaction between the driver groups aquaculture and agriculture and industrialization and pollution. Our results suggest prioritizing globally coordinated empirical studies linking drivers and mangrove deforestation and global development of policies for mangrove conservation.