The Tarim River, the largest inland river in China, sits in the Tarim River Basin (TRB), which is an arid area with the ecosystem primarily sustained by water from melting snow and glaciers in the headstream area. To evaluate the pressures of natural disasters in this climate-change-sensitive basin, this study projected flash droughts in the headstream area of the TRB. We used the variable infiltration capacity (VIC) model to describe the hydrological processes of the study area, Markov chain Monte Carlo to quantify the parameter uncertainty of the VIC model. Ten downscaled general circulation models from the Coupled Model Intercomparison Project Phase 6 (CMIP6) were used to drive the VIC model, and the standardized evaporative stress ratio was applied to identify flash droughts. The results demonstrated that the VIC model after Bayesian parameters uncertainty analysis can efficiently describe the hydrological processes of the study area. In the future (2021–2100), compared with the plain region, the alpine region has higher flash drought frequency and intensity. Compared with the historical period (1961–2014), the frequency, duration, and intensity of flash droughts tend to increase throughout the study area, especially for the alpine area. Moreover, based on variance decomposition, CMIP6 model is the most important uncertainty source for flash drought projection, followed by the shared socioeconomic pathway of climate change scenario and VIC model parameters. Key Points The hydrological processes of study area are well described by the variable infiltration capacity model and Bayesian uncertainty analysis Compared with the plain region, the alpine region has higher flash drought frequency and intensity in the future The Coupled Model Intercomparison Project Phase 6 model is the most important uncertainty source for flash drought projection Plain Language Summary The Tarim River is the largest inland river in China, which is an arid area with the ecosystem primarily sustained by water from melting snow and glaciers in the headstream area. Compared with long-duration drought, flash drought is more difficult to forecast and identify. We used the variable infiltration capacity model to build a hydrological model of the headstream area of the Tarim River Basin, and the model output (ET data) was used to identify flash droughts. Based on 10 representative Coupled Model Intercomparison Project Phase 6 (CMIP6) models, this study projected the future flash droughts in the study area under climate change. The findings indicated that the alpine region is likely to experience a greater frequency and intensity of flash droughts in the future (2021–2100) compared to the plain region. Compared with the historical period (1961–2014), the frequency, duration, and intensity of flash droughts tend to increase throughout the study area, especially for the alpine area. In addition, the result of uncertainty decomposition revealed that the CMIP6 model is the most important uncertainty source for flash drought projection.