The Atlantic Meridional Overturning Circulation (AMOC) plays an important role in regulating the global climate. The AMOC change in response to global warming has important environmental and, potentially, societal impacts but remains an issue with large uncertainty. Here we use a series of coupled climate model experiments to reveal the overlooked role of Atlantic subtropical salinification, a robust consequence of an intensified hydrological cycle, in inhibiting AMOC weakening under global warming. Without subtropical salinification, the AMOC weakening more than doubles in response to a doubling of CO2, primarily driven by a reduced zonal salinity gradient that weakens the geostrophic component of AMOC through the thermal wind relation. This larger AMOC weakening reduces surface warming in the Northern Hemisphere by as much as 1–3 K at northern high latitudes when subtropical salinification is inhibited.