Prior to joining the administration of George H. W. Bush, O'Keefe was the Louis A. Bantle Professor of Business and Government Policy, an endowed chair at the Syracuse University Maxwell School of Citizenship and Public Affairs. He was also a Professor of Business Administration and Assistant to the Senior Vice President for Research and Dean of the Graduate School at Pennsylvania State University.
Before serving as Secretary of the Navy, O'Keefe had been Comptroller and Chief Financial Officer of the Department of Defense since 1989. Before joining the Department of Defense, he served on the United States Senate Committee on Appropriations staff for eight years, and was Staff Director of the Defense Appropriations Subcommittee.
Since taking over Nasa, O'Keefe has been criticized as a "bean counter" - someone who has no vision of space exploration.