On June 5, 2001, Jeffords left the Republican Party, with which he had always been affiliated, and announced his new status as an Independent. This occurred despite, for example, Jefford's voting for President Bush's tax cut package along with all other Republicans in May 26, 2001. Jeffords's Independent status changed the Senate composition from 50-50 (with a Republican Vice President, Dick Cheney, who would break all ties in favor of the Republicans) to 49 Republicans, 50 Democrats, and one Independent. Jeffords promised to vote for Democratic control after being promised a committee chairmanship by Democratic Leader Tom Daschle, thus handing control of the Senate to the Democrats. He then handed his chairmanship of the Health, Education, Labor, and Pensions Committee, which he had held since 1997, to Ted Kennedy (D-MA) and was given the chairmanship of the Senate Environment and Public Works Committee, which would have been occupied by ranking minority member Harry Reid. Jeffords held this committee chair until the Democrats lost control of the Senate in 2003 following Congressional elections in 2002.
Jeffords made a deal with the Democrats according to which he votes with them on all procedural matters except with permission of the Whip, which would be rarely asked and rarely granted, in exchange for the committee seats that would have been available to Jeffords had he been a Democrat during his entire Senate tenure. Jeffords is free to vote as he pleases on substantive matters but more often than not votes with the Democrats. Even before his party switch, his voting record was very liberal, which is typical for Republicans from Vermont. While a Republican he voted for the Civil Rights Act of 1991, the Brady Bill, the Family and Medical Leave Act, an end to the ban on gays serving in the military, and against permanent normal trade relations with China. Jeffords was also vocal in his opposition to the nomination of Clarence Thomas to the United States Supreme Court by President George H.W. Bush. He was the only prominent Republican to support President Clinton's failed attempt to establish a national healthcare plan. His position put him to the political left of many Democrats who had serious doubts about Clinton's plan.
On October 11, 2002, Jeffords was one of only 23 senators to vote against authorizing the use of military force in Iraq. On this issue of foreign policy and other issues, Jeffords has strongly disagreed with the positions of the Bush administration.