Monitoring human activities in border areas is challenging due to the complex geographical environment and diverse people. China has the longest terrestrial boundary and the highest number of neighboring countries in the world. In this study, a human activity intensity index (HAI) was proposed based on land cover, population density, and satellite-based nighttime light for a long-term macroscopic study. The HAI was calculated at 1 km resolution within the 50 km buffer zone of China’s land boundary on each side in 1992, 2000, 2010, and 2020, respectively. Results show that human activity is low in about 90% of the study area. Overall, the HAI on the Chinese side is higher than that on the neighboring side, and the intensity of land use on the Chinese side has increased significantly from 1992 to 2020. Among China’s neighbors, India has the highest HAI with the fastest growth. With the changes in the HAI between China and its neighboring countries, four regional evolution patterns are found in the study area: Sino-Russian HAI decline; Sino-Kazakhstan HAI unilateral growth; Indian HAI continuous growth; China and Indochina HAI synchronized growth. Hotspot analysis reveals three spatial evolution patterns, which are unilateral expansion, bilateral expansion, and cross-border fusion. Both the “border effect” and “agglomeration effect” exist in border areas. The HAI changes in border areas not only impact the eco-environment but also affect geopolitics and geoeconomics. The HAI can be used as an instrument for decision-making and cooperation between China and neighboring countries in such areas as ecological protection, border security, and border trade.