The Dongting Lake Basin is an important hydrological regulation and flood storage area in the Yangtze River Basin, which plays an important role in maintaining regional ecological security. The watershed vegetation and its carbon sequestration capacity have changed dramatically due to climate change and human activities in the last two decades. In this paper, the monthly and annual vegetation net primary productivity (NPP) of the Dongting Lake basin during 2000 to 2020 was firstly estimated using the improved Carnegie-Ames-Stanford Approach (CASA) model. Then the multi-year NPP change trend and its significance were analyzed based on Theil-Sen median and Mann-Kendall method. Subsequently, the Hurst index was used to simulate the vegetation NPP persistence in the study area. Finally, the driving mechanisms of vegetation NPP changes in the study area were explored using partial correlation coefficients and residual analysis. The results demonstrated that: 1) The annual average NPP in the basin showed a fluctuating and increasing trend from 273.54 to 718.30 g C/m2·yr1 during 2000 to 2020, and except for autumn, all seasons (spring, summer, winter) and annual NPP series showed an upward trend. The spatial distribution of vegetation NPP is characterized by an asymmetrical horseshoe shape in general, with high values in the west, south and east parts, and low values in the Lake area; 2) During the study years, about 84.38 % of the basin area showed a significant and extremely significant increase of NPP; 3) The future trend of vegetation NPP in the basin shows that the area of decrease (22.79 %) is more than the area of increase (11.35 %). The Chang-Zhu-Tan urban agglomeration will generally show a continuous and extremely significant reduction trend, while parts of Dongting Lake will show a continuous and extremely significant increase trend; 4) The correlation between solar radiation and NPP is stronger than the other two meteorological factors (precipitation and temperature). Temperature has a significant inhibitory effect on NPP, solar radiation has a significant promoting effect on NPP, and the effect of precipitation on NPP was relatively complicated. The relative importance of meteorological factors on vegetation NPP was ranked as follows: solar radiation > precipitation > temperature. The impacts of both climate change and human activities on NPP changes showed great spatial variability, and the positive contributions (89.81 % for climate change and 82.87 % for human activities) were both greater than the negative contributions.