Since the reform and opening-up program started in 1978, the level of urbanization has increased rapidly in China. Rapid urban expansion and restructuring have had significant impacts on the ecological environment especially within built-up areas. In this study, ArcGIS 10, ENVI 4.5, and Visual FoxPro 6.0 were used to analyze the human impacts on vegetation in the built-up areas of 656 Chinese cities from 1992 to 2010. Firstly, an existing algorithm was refined to extract the boundaries of the built-up areas based on the Defense Meteorological Satellite Program Operational Linescan System (DMSP_OLS) nighttime light data. This improved algorithm has the advantages of high accuracy and speed. Secondly, a mathematical model (Human impacts (HI)) was constructed to measure the impacts of human factors on vegetation during rapid urbanization based on Advanced Very High Resolution Radiometer (AVHRR) Normalized Difference Vegetation Index (NDVI) and Moderate Resolution Imaging Spectroradiometer (MODIS) NDVI. HI values greater than zero indicate relatively beneficial effects while values less than zero indicate proportionally adverse effects. The results were analyzed from four aspects: the size of cities (metropolises, large cities, medium-sized cities, and small cities), large regions (the eastern, central, western, and northeastern China), administrative divisions of China (provinces, autonomous regions, and municipalities) and vegetation zones (humid and semi-humid forest zone, semi-arid steppe zone, and arid desert zone). Finally, we discussed how human factors impacted on vegetation changes in the built-up areas. We found that urban planning policies and developmental stages impacted on vegetation changes in the built-up areas. The negative human impacts followed an inverted’ U’ shape, first rising and the falling with increase of urban scales. China’s national policies, social and economic development affected vegetation changes in the built-up areas. The findings can provide a scientific basis for municipal planning departments, a decision-making reference for government, and scientific guidance for sustainable development in China.