This paper provides the first wide-area Interferometric Synthetic Aperture Radar (InSAR) survey of the whole eastern Trans-Mexican Volcanic Belt (42,200 km2). The aims are to identify ground deformation hotspots within major urbanized areas and rural valleys, establish baselines in geothermal exploration sites, and analyze deformation at geothermal exploitation sites and its relationship with energy production. The whole 2003–2010 ENVISAT C-band SAR archive available over the region was processed with the Small BAseline Subset (SBAS) InSAR method to retrieve over 840,000 coherent targets and estimate their ground displacement rates and time series. Land subsidence hotspots due to aquifer drawdown are found within the city of Puebla (up to −53 mm/year vertical rates, groundwater pumping for industrial use), Tlaxcala and Apizaco (−17 mm/year, industrial and public), the valley of Tecamachalco (−22 mm/year, agricultural), Tulancingo (−55 mm/year, public, industrial and agricultural), and in the eastern Mexico City metropolitan area (−44 mm/year, agricultural). The baseline for the Acoculco caldera complex shows widespread ground stability. Conversely, localized subsidence patterns of −5 to −10 mm/year exist around Las Derrumbadas and Cerro Pinto in the Serdán-Oriental basin, due to intense groundwater pumping for agriculture. A well-defined land subsidence area with −11 mm/year maximum rates is found at Los Humeros volcanic complex within Los Potreros collapse, correlating well with energy production infrastructure location and historical steam production rates. Field surveys carried out in Acoculco and Los Humeros in 2018 provide supporting evidence for the identification of hydrothermal manifestations, and understanding of the landscape and surface deformation patterns within the geothermal fields.