Ecosystem services are closely associated with human well-being, and a supply–demand mismatch of ecosystem services will be detrimental to sustainable development, particularly in developing regions. The Qinghai–Gansu–Ningxia region in northwestern China is a typical developing area with abundant natural resources but a relatively underdeveloped economy. This study quantified the supply, demand, and supply–demand ratio for carbon sequestration, water yield, and food production from 2000 to 2020, and analyzed the driving mechanisms and flow potential of key ecosystem services in the Qinghai–Gansu–Ningxia region. It was found that carbon sequestration demand, food production supply, and food production demand gradually increased, whereas water yield demand gradually decreased. The supply–demand imbalance of key ecosystem services was severe in some regions. With slowing population growth and increasing food output, the supply–demand imbalance of food production gradually improved from 2000 to 2020. The supply–demand balance of food production was more influenced by socioeconomic factors, whereas the supply–demand balance of carbon sequestration and water yield was more influenced by ecological factors. Moreover, the flow potential of carbon sequestration tended to manifest as short-distance transfers from neighboring regions, while the flow potential of water yield and food production tended to be outward transfers from high supply areas. These findings could enhance understanding of key ecosystem services based on a supply–demand perspective, which will facilitate effective resource allocation and promote synergistic development across regions, and will have implications for ecological management in similar developing regions.