Although previous studies have estimated the effects of human regulations on hydrological drought, few studies have examined the impacts from the perspective of the development and recovery processes of hydrological drought. This study uses the Dongjiang River Basin in south China as an example and focuses on the influence of reservoir operation on hydrological drought. The Standardized Streamflow Index (SSI) and run theory were applied to determine the development and recovery processes of hydrological drought. A semi-distributed hydrological model, the Soil and Water Assessment Tool (SWAT), was used to simulate long time series (>30 years) monthly streamflow data; the SWAT model was calibrated and validated using the monthly streamflow data from periods with less human regulations. Streamflow was then simulated and compared by using the same model parameters, as well as the sub-surface features, to simulate the streamflow during the human regulation periods. The “simulated-observed” comparative approach (i.e., a comparison of the characteristics of the hydrological drought obtained from the simulation-based SSI and observation-based SSI) was used to assess the impacts of human regulations on hydrological drought development and recovery. The results showed that the ‘simulated-observed’ comparison approach based on the SWAT model exhibited a good ability to ascertain the impacts of human regulations on hydrological drought development and recovery. The reservoir operation was the dominant factor affecting the hydrological drought propagation in the lower reaches of the Dongjiang River basin and had mostly a short-term effect by decreasing the duration and severity of drought development (or recovery). However, the reservoirs tended to release water during the development process and to store water during the recovery process during a long-term hydrological drought in the study area, leading to an increase in average recovery duration and severity. The results of this study may further optimize water resources management system during drought for effective drought prevention and mitigation.