Wildfires have profound impacts on the environment and human societies. Investigating the relationships among wildfires, vegetation, and climate is critical to understanding long-term wildfire patterns and predicting future wildfire risks. A Th-230/U-dated, similar to 24-year resolution stalagmite stable isotope (delta O-18 and delta C-13) record from Dongge Cave, Guizhou Province, provides us with the history of the monsoonal precipitation and vegetation evolution in southwestern China from 10.9 to 4.6 ka BP, covering the Early to Mid Holocene. We interpret our delta O-18 and delta C-13 records and correlate them with reconstructions of wildfire activity from the monsoonal region of China, intending to discuss the vegetation-fire-climate interactions and possible causal mechanisms. The results indicate that during the Early Holocene, wildfire activity was relatively suppressed by the enhanced summer monsoon rainfall, humid conditions, and vegetation expansion. During the Mid Holocene, when the Asian summer monsoon weakened, the regional climate was dry, the vegetation gradually deteriorated (with herbaceous plants replacing evergreen and C4 vegetation), and wildfire activity significantly increased. The decline of solar insolation and increasing CO2 concentration during the Mid Holocene triggered a monsoon deterioration through atmospheric teleconnections and southward movement of the Intertropical Convergence Zone. The increased frequency of El Ni & ntilde;o-Southern Oscillation at around 7.8, 6.3, and 4.9 ka BP during the Mid Holocene further caused Asian summer monsoon weakening and exacerbated aridification in the monsoonal region of China, which likely contributed to the dynamics of wildfires.