•Tree-ring δ18O network indicates an east–west clustering pattern.•Regional variability of tree-ring δ18O is regulated by hydroclimatic changes.•Different patterns of tree-ring δ18O variability represent different moisture signals.•El Niño-Southern Oscillation modulates δ18Otree variability across southern China. The East Asian summer monsoon (EASM) and Indian summer monsoon (ISM) are two interactive climate systems dominating the moisture variability of Monsoon Asia. However, ISM-EASM interactions and their effects on regional moisture dynamics remain unclear. This study investigated the spatiotemporal characteristics of monsoon-related hydroclimate variability by establishing a new tree-ring oxygen isotope ratio (δ18Otree) network of eight δ18Otree records covering the last 150 years in southern China, which differs from previous studies that used data from individual sites. The δ18Otree chronologies were found to be sensitive to regional hydroclimatic changes during the monsoon season. The δ18Otree network indicated an east–west clustering pattern in the ISM-EASM transitional zone, which demonstrates an asynchrony in δ18Otree variability in the west and east of this region. Regional variability of the west and east δ18Otree modes reflected the different moisture signals, as indicated by their significant correlations with modern observations and paleo-δ18O records in disparate upstream regions of moisture transport (the Indochina Peninsula and Southeast China). This finding was confirmed by the east–west distinct pattern of spatial isotopic depletion of monsoon rainfall that originates from coastal areas of tropical oceans (Bay of Bengal and South China Sea) to the study area, as well as the consistent present-day pattern of atmospheric vapor transport during the monsoon season. In addition, the west and east modes exhibited stronger associations with ISM variability, whereas the east–west δ18Otree gradient captured the EASM-related hydroclimatic signal, suggesting that summer moisture variability in the ISM-EASM transitional zone was regulated more by ISM than by EASM during the last 150 years. The relationships between δ18Otree and large-scale ocean–atmosphere interaction modes revealed that the El Niño-Southern Oscillation (ENSO) dominantly modulates δ18Otree variability across southern China.