A large portion of lakes on the Tibetan Plateau (TP) have experienced considerable expansion in the past decades. However, how the lake surface area expansion has influenced regional precipitation, especially its underlying mechanism, has not been investigated. By selecting the most dramatically expanded lake on the TP as a case study, this paper investigates the magnitude and extent of the precipitation response to lake expansion and its underlying mechanism using twin Weather Research and Forecasting (WRF) simulations with and without lake expansion. The results show that the precipitation response to the lake expansion exhibits pronounced spatial and seasonal variations and is generally more intense in the downwind direction than in the upwind direction. During the wet season (the South Asian summer monsoon, SASM), precipitation decreases in the downwind area by −25% ± 16% and −13% ± 15% in the 0–50 km and 50–100 km intervals (from the lake’s center), respectively. Conversely, the precipitation increases in the downwind area during the dry season (before the freeze and after the SASM) by 27% ± 36% in the 0–50 km interval. The thermal and evaporative effects, which are generated by lake expansion and propagate in the downwind direction, are the key factors responsible for the precipitation changes. The cooling effect, which generally occurs in the daytime, stabilizes the atmosphere and triggers downward motion, consequently inhibiting precipitation. The warming effect has the opposite effect, and the additional water vapor strengthens this process. However, the effects vary with the seasons, causing seasonal variations in the precipitation response.