Abstract Precipitation isotopes (δ 18 O) offer valuable insights into the climate of the Tibetan Plateau (TP) across different timescales. However, synoptic‐scale variations in precipitation δ 18 O are rarely discussed. This study presents synoptic‐scale variations in precipitation δ 18 O induced by the Indian monsoon depression (MD) during June‐September. The MD drives intense convection and rainfall over India, playing a crucial role in upstream processes on the TP. We use daily precipitation δ 18 O from four sites along a south‐north profile on the southern TP, spanning 92 MD events (1997–2018), and apply machine learning to rank the influencing climate factors. Results show clear spatial differences in precipitation δ 18 O response to synoptic events on the TP. During the MD, precipitation δ 18 O decreases significantly on the southern side of the Himalayas but slightly increases on the northern side. On the southern side, lower precipitation δ 18 O is resulted from an increase in westward water vapor flux while higher δ 18 O in the north is associated with an increase in southward water vapor flux and a decrease in the intensity of water vapor flux. Precipitation δ 18 O strongly depends on upstream rainfall and convection during the MD events on the southern side of the Himalayas, but less on the northern side. A positive correlation between precipitation δ 18 O and the El Niño‐Southern Oscillation index is observed in the Asian Summer Monsoon region, though the MD activity weakens this correlation on the southern side of the Himalayas. Our findings clarify the understanding of precipitation δ 18 O in a synoptic scale system on the southern TP.