The origin of C4 agriculture in China, foxtail millet (Setaria italica) and common millet (Panicum miliaceum), remains unclear. Here we conducted a comprehensive geochemical study of the archeological site of Chahai in Northeastern (NE) China and deduced that higher C4 biomass in the cultural layers was mainly caused by agricultural practices and other human activities. To evaluate the anthropogenic factors involved in millet domestication, we produced a time series of contour maps of C4 biomass for North China since 14 ka and integrated archaeological data. Results show that the origin and development of millet agriculture was nearly synchronous with the increase in C4 biomass in the early-mid Holocene, but the synchrony was decoupled at 4 ka when millet cultivation was established in NE China. Our findings suggest that both human management (possibly cultivation) of C4 plants, and an environmental background of high C4 biomass drove the origin of millet agriculture.