The impact of climate change on human social development and civilizational evolution in the Holocene has been widely recognized by researchers. During the arid conditions of the late Holocene, the Siba and Shajing cultures flourished in the Hexi Corridor at the northeastern edge of the Qinghai-Xizang Plateau. This occupation may be closely related to a short-term humid climate; however, the climate change patterns in the Hexi Corridor since the Holocene and their possible impact on human remain unclear. In this study, we acquired three lake sections in the Hexi Corridor and integrated paleoclimate records from surrounding areas, radiocarbon dates from human and animal bones, and plants from archaeological sites to investigate the relationship between human activity and climate change in the Hexi Corridor. The results indicate that the eastern and western regions of the Hexi Corridor experienced humid periods during different periods of the mid-Holocene, which were influenced by the East Asian summer monsoon and Westerly jet, and the climate in the Hexi Corridor was generally arid during the late Holocene. During the period of similar to 4300-3700 cal yr BP, increased humidity and cultural exchanges promoted the development of agriculture and animal husbandry at the western end of the Hexi Corridor, and the Siba culture flourished during this period. A brief humid period occurred in the eastern section of the Hexi Corridor during the period of similar to 2500-2300 cal yr BP, providing the conditions for the development of animal husbandry in the Shajing culture. Our research suggests that there is a close correlation between humid climates and the flourishing of ancient cultures, particularly in arid and semi-arid regions.