Using the multivariate EOF analysis performed on the observation datasets, this study reveals that the Greater Mekong Subregion (GMS) has been toward warm-dry springs over most regions especially after the 2000s, accompanied by increased surface temperature and decreased precipitation anomalies. Such climate condition provides favourable environment for compound heat and drought events, raising questions about how the spring climate in GMS will change as climate warms. Based on a multi-model weighting scheme among CMIP6 models, we project the regional climate changes in GMS in a warmer world under the SSP5–8.5 scenario. Results show that the southern GMS including Vietnam, Laos, Thailand, and Cambodia will become warmer-drier throughout the 21st century in response to global warming. In contrast, the climate condition over the northern GMS including Myanmar and Yunnan province of Southwest China is expected to experience a transition from dry to wet springs in a warmer world, resulting in a tendency toward the warm-wet springs particularly in the long-term future. This knowledge indicates the spatial non-uniformity of regional climate under global warming and will aid in advance to plan for water management and agricultural adaptation.