Urbanization is causing profound changes in ecosystem functions at local and regional scales. The net primary productivity (NPP) is an important indicator of global change, rapid urbanization and climate change will have a significant impact on NPP, and urban expansion and climate change in different regions have different impacts on NPP, especially in densely populated areas. However, to date, efforts to quantify urban expansion and climate change have been limited, and the impact of long-term continuous changes in NPP has not been well understood. Based on land use data, night light data, NPP data, climate data, and a series of social and economic data, we performed a comprehensive analysis of land use change in terms of type and intensity and explored the pattern of urban expansion and its relationship with NPP and climate change for the period of 2000–2015, taking Zhengzhou, China, as an example. The results show that the major form of land use change was cropland to built-up land during the 2000–2015 period, with a total area of 367.51 km2 converted. The NPP exhibited a generally increasing trend in the study area except for built-up land and water area. The average correlation coefficients between temperature and NPP and precipitation and NPP were 0.267 and 0.020, respectively, indicating that an increase in temperature and precipitation can promote NPP despite significant spatial differences. During the examined period, most expansion areas exhibited an increasing NPP trend, indicating that the influence of urban expansion on NPP is mainly characterized by an evident influence of the expansion area. The study can provide a reference for Zhengzhou and even the world's practical research to improve land use efficiency, increase agricultural productivity and natural carbon sinks, and maintain low-carbon development.