This study investigated the water regime changes and the associated driving factors of Dongting Lake in the normal and dry seasons. The long short-term memory network modeled the outflow and water level of Dongting Lake, and the driving factors of water regime variation were detected using scenario simulation. From 1992 to 2019, the outflow of Dongting Lake in September and October decreased dramatically, caused by the reduced flow of the Yangtze River. The water level of Dongting Lake during the normal and dry seasons mainly lowered. The average water level in September and October dropped by 1 m in West and South Dongting Lake, while it dropped by 2 m in East Dongting Lake. Morphologic changes mainly lowered the water level during the normal and dry seasons. Flow changes of the Yangtze River and the four tributaries of the Dongting Lake basin dropped the water level in September and October and elevated the water level from December to March of the following year. The impact of flow changes on the water level of East Dongting Lake was relatively more significant. The results provided implications for water resources management and wetland protection of Dongting Lake in the normal and dry seasons.