Human activities involving nature have various environmental impacts. The assessment of the spatial and temporal evolution of human activity intensity (HAI) and its driving forces is significant for determining the effects of human activities on regional ecological environments and regulating such activities. This research quantified the HAI of China, assessed its spatiotemporal characteristics, and analyzed its influencing factors based on the land use data and panel data of 31 provinces in mainland China. The results indicate that the HAI in China is increasing, with the average value increasing from 15.83% in 1980 to 20.04% in 2018, and the HAI was relatively serious in the Beijing–Tianjin–Hebei region, Yangtze River Delta and Pearl River Delta in this period. The spatial differences in the HAI in China show a pattern of being strong in the east and weak in the west, and the spatial center of gravity of China’s HAI has gradually moved west, changing from a central enhancement mode to a point-like “core” enhancement mode. The dominant factors affecting spatial differences in HAI are economic and industrial levels. Labor, population, and capital factors also strongly impact HAI, and energy consumption and pollution emissions have little impact. These results deepen the understanding of the underlying mechanism of the environmental impact of human activities and provide a scientific basis for land-use-related decision making and eco-environment construction.