Asia’s high plateaus are sensitive to climate change and have been experiencing rapid warming over the past few decades. We found 99 new lakes and extensive lake expansion on the Tibetan Plateau during the last four decades, 1970–2013, due to increased precipitation and cryospheric contributions to its water balance. This contrasts with disappearing lakes and drastic shrinkage of lake areas on the adjacent Mongolian Plateau: 208 lakes disappeared, and 75% of the remaining lakes have shrunk. We detected a statistically significant coincidental timing of lake area changes in both plateaus, associated with the climate regime shift that occurred during 1997/1998. This distinct change in 1997/1998 is thought to be driven by large-scale atmospheric circulation changes in response to climate warming. Our findings reveal that these two adjacent plateaus have been changing in opposite directions in response to climate change. These findings shed light on the complex role of the regional climate and water cycles and provide useful information for ecological and water resource planning in these fragile landscapes.