[Objective] The spatial-temporal variation of terrestrial vegetation coverage in Lugu Lake Wetland Nature Reserve in Sichuan Province during 2000—2020 was analyzed in order to provide a reference for the construction and management of the reserve. [Methods] MODIS data from June to September of 2000—2020 for the Lugu Lake Wetland Nature Reserve in Sichuan Province was the data source. Correlation analysis methods such as pixel dichotomy and Theil-SenMedian trend analysis were combined to determine the spatial-temporal variation characteristics of vegetation coverage and their response to climate. [Results] ① The overall terrestrial vegetation coverage of Lugu Lake Wetland Nature Reserve in Sichuan Province slightly increased from 2000 to 2020, and increased at a rate of 0.09/10 yr. ② Vegetation coverage of the protected area was low in the lake area and the surrounding areas, and higher in the north and south areas. The spatial variation of vegetation coverage of the protected area increased overall but decreased locally. ③ The climate of the reserve (from June to September) tended to be “warmer and drier”, and fractional vegetation coverage was mainly positively correlated with temperature and precipitation. The influence of temperature was greater than that of precipitation. The specific influencing factors had spatial differences. [Conclusion] From 2000 to 2020, the vegetation coverage of the Lugu Lake Wetland Nature Reserve in Sichuan Province was good, and the vegetation coverage slightly increased over time. Temperature was the main climate factor affecting vegetation coverage. Topography and human activities, meanwhile, had some effects on the vegetation coverage of the reserve to a certain extent.