Land use and land cover change (LUCC) has a significant influence on regional net primary productivity (NPP) in territorial ecosystems. Evaluating the driving factors of LUCC and the influences of LUCC on NPP is significant for understanding the driving mechanisms deeply and improve land management. NPP as estimated by the Carnegie–Ames–Stanford Approach (CASA) model was employed as an important indicator to evaluate the influences of LUCC on regional NPP and decouple interactive effects of LUCC and climate change on NPP in Anhui from 2001 to 2010. The results demonstrated that 34.25% of the whole area had occurred in LUCC. The most dominant transformation of LUCC was the conversion from grassland and crop/natural vegetation mosaic to forest and cropland. The area of cropland and forest had the most increments compared to other land use types, with an increase of 30.52% and 35.29% of that in 2001. Socio-economic development, economic interests and government policies took an important role in driving the LUCC. The total NPP increased mainly due to the contributions of the area expansion of cropland and forest. Climate change resulted in the decreased NPP of 449.84 GgC, whereas LUCC facilitated the NPP in the increase of 1816.05 GgC. This result indicates that the increased NPP induced by LUCC could offset the NPP decrease from climate change during the study periods. This paper also demonstrated that reforestation and forest protection were indeed effective in promoting ecosystem productivity.