Net primary productivity (NPP) of vegetation is an important indicator of the carbon balance in terrestrial ecosystems. Studying the impact of climate change and human activities on NPP is of great significance for achieving carbon neutrality goals and improving ecosystem functions. Based on MOD17A3HGF data, meteorological data, DEM data, and land cover type data, this paper analyzed the spatiotemporal distribution pattern and trend characteristics of vegetation NPP in Chongqing from 2001 to 2020, using trend analysis and partial derivative analysis methods. The contribution of climate factors and human activities to NPP changes was quantified, and the driving factors of NPP changes were explored. The results showed that: (1) From 2001 to 2020, the average value of NPP in Chongqing was 620.29 gC m-2, and the spatial distribution of vegetation NPP showed a gradually increasing pattern from southwest to northeast along the Yangtze River. (2) In the past 20 years, the overall NPP in Chongqing changed at a rate of 5.38 gC m-2a-1, with a significant increase trend. The area proportions of increasing and decreasing trends in NPP in karst areas were 90.04% and 9.96%, respectively. (3) The contribution of climate change to NPP changes in Chongqing during the study period was greater than that of human activities, and the negative impact of human activities on NPP changes was more significant. The NPP changes in non-karst areas were mainly influenced by climate, and the negative effects of human activities on NPP changes accounted for a larger proportion. The contribution of climate change and human activities to NPP changes in karst areas was comparable, with the negative impact of climate factors on NPP changes accounting for a larger proportion (33.11%) than human activities (28.51%). The implementation of ecological engineering promoted the improvement of NPP. (4) The driving force analysis showed that the NPP changes in the study area were mainly driven by climate and human activities, but there existed significant spatial differences. The increase of NPP in the west and northeast of Chongqing was mainly driven by climate and human activities. The increase of NPP in central Chongqing was primarily driven by climate change. The increase of NPP in southeast Chongqing and other karst areas was more obviously dominated by human activities, while the negative effect of climate conditions on vegetation NPP in karst areas was more evident.