In 2000, Bush nominated Paul O'Neill, a man with extensive experience in the business and public worlds, to become his treasury secretary. Paul H. O'Neill was born in St. Louis, Missouri, in 1935 and worked briefly as an engineer in Alaska before finishing his education. He graduated from Fresno State in California in 1960 and did course work at Claremont Graduate School and George Washington University before earning his master of public administration from Indiana University. O'Neill's career in the public sector began with a stint working on veteran affairs from 1961 to 1966. From 1967 to 1977, he signed on with the Office of Management and Budget (OMB), ultimately rising to the level of deputy director from 1974 to 1977. After leaving OMB, O'Neill worked with the International Paper Company in New York; when he left the firm in 1987, he had been president and director of the company for two years.

Named chief executive officer of Alcoa, O'Neill spent the next thirteen years turning the large aluminum producer into an industry superpower, reaching over $16 billion in sales by 1999. During the same period, O'Neill served as chair of the President's Education Policy Advisory Commission (1989-1992) and was active with, among other civic organizations, the American Academy of Arts and Sciences, the Gerald R. Ford Foundation, and the H. John Heinz III Center for Science.

Paul O'Neill resigned as secretary of the treasury in 2002.