In the 2000 election, Holden narrowly defeated RepublicanJim Talent. Holden was inaugurated as governor in January 2001. His inauguration was the most elaborate and expensive in state history. The ceremony cost $1 million, of which $125,000 was paid from state government funds. Although Holden's inauguration ceremony received public financing equal to that of Missouri's previous two Governors, a perception that the inauguration was overly extravagant emerged and became a theme in opposition to his administration. Holden was a member of the National Governors Association and was elected chair of the Midwestern Governors’ Conference which led the Midwestern states’ efforts to stimulate the economy by focusing on education and research. He also chaired the Governor's Ethanol Coalition and represented fellow governors on the National Medicaid Reform Task Force. Holden repeatedly defended Missouri's Medicaid program from cuts by the Republican legislature. In 2001, Holden called a special session to create Missouri's Senior Rx Program. Holden was pro-gun, but due to some negative effects that he felt proposed legislation would have on Missouri gun owners, he vetoed a concealed-carry bill passed by the Missouri General Assembly. This was short-lived because his veto was overridden by both the Missouri House of Representatives and Senate and the concealed-carry bill passed into law in 2003. Several Republican legislators who had initially voted against the bill, including Michael Gibbons of Kirkwood, switched sides to override Holden's veto. Holden favored greater spending on state elementary and secondary education. At one point in his term, he called the state legislature back into session after they had recessed for the year to ask for more state funding for education, but they refused additional monies. Holden served as a Chair of the Midwestern Governors Association in 2003. Holden's term as governor ended on January 10, 2005.
In 2004, as Holden sought re-election, he was challenged for the Democratic nomination for governor by a fellow Democrat, State AuditorClaire McCaskill. McCaskill successfully tapped into broad-based disgruntlement with Holden that prompted even some Democrats to call him by the unflattering moniker "OTB". After Holden's approval rating steadily dropped during the second half of his term, McCaskill defeated Holden in the Democratic primary, marking the first primary loss for a sitting governor in nearly two decades. McCaskill was herself defeated in the November 2 general election by Republican Secretary of StateMatt Blunt.
Life after politics
Holden now teaches political science and communications courses at Webster University. Governor Holden is the founder and Director of the Holden Public Policy Forum at Webster University. The Forum describes itself as "a bi-partisan speakers series that will bring Governors, Senators, presidential candidates and private sector public policy leaders to St. Louis and the Webster University Old Post Office campus." Governor Holden serves as Chairman of the United States Heartland China Association, a non-profit organization that works with the Chinese People's Association for Friendship with Foreign Countries to encourage trade between 12 states in the Midwestern United States and China. Holden endorsed Senator Hillary Clinton in the Democratic primaries of the 2008 presidential campaign and served as a Missouri Co-Chair and a member of the Clinton campaign's Education Policy Taskforce.