Returning to government service in 1940, Clayton first Later in World War II, he took on a number of roles in the Roosevelt and Truman administrations. He first served as deputy to the coordinator of inter-American affairs. For the next four years he held a variety of high-level positions with the Export-Import Bank, the Department of Commerce, and wartime agencies. He served as assistant, and then as deputy Secretary of State for economic affairs from December 1944 to October 1947, where he was primarily concerned with working on the Marshall Plan. He returned to Houston and private life in late 1947, though he continued to serve the government as a participant and contributor to various international conferences on world trade and other economic issues.