"He will take office with the weakest support of any defense secretary in modern history, which will make him less effective on his job," said Sen. John Cornyn of Texas, the Senate GOP's No. 2 Republican.
Not so, said Democratic Sen. Jack Reed, who pointed out that Hagel now has the title and the fight is history.
"All have to work together for the interest of the country," said Reed, D-R.I.
The vote ended one of the most bitter fights over a Cabinet choice and former senator since 1989 when the Democratic-led Senate defeated newly elected President George H.W. Bush's nomination of Republican John Tower to be defense secretary.
In the course of the rancorous, seven-week nomination fight, Republicans, led by freshman Sen. Ted Cruz of Texas and Sen. Jim Inhofe of Oklahoma, insinuated that Hagel has a cozy relationship with Iran and received payments for speeches from extreme or radical groups. Those comments drew a rebuke from Democrats and some Republicans.
Sen. Carl Levin, D-Mich., the chairman of the Armed Services Committee, dismissed the "unfair innuendoes" against Hagel and called him an "outstanding American patriot" whose background as an enlisted soldier would send a positive message to the nation's servicemen and women.
Sen. Claire McCaskill, D-Mo., questioned how the confirmation process devolved into a character assassination in which Hagel was accused of "having secret ties with our enemies."
"I sincerely hope that the practice of challenging nominations with innuendo and inference, rather than facts and figures, was an aberration and not a roadmap," she said in a statement after the vote.
Obama got no points with the GOP for tapping the former two-term Republican senator. Republican lawmakers excoriated Hagel and cast him as a radical far out of the mainstream.
McCain clashed with his onetime friend over his opposition to Bush's decision to send an extra 30,000 troops to Iraq in 2007 at a point when the war seemed in danger of being lost. Hagel, who voted to authorize military force in Iraq, later opposed the conflict, comparing it to Vietnam and arguing that it shifted the focus from Afghanistan.
Republicans also challenged Hagel about a May 2012 study that he co-authored for the advocacy group Global Zero, which called for an 80 percent reduction of U.S. nuclear weapons and the eventual elimination of all the world's nuclear arms.
The group argued that with the Cold War over, the United States could reduce its total nuclear arsenal to 900 without sacrificing security. Currently, the U.S. and Russia have about 5,000 warheads each, either deployed or in reserve. Both countries are on track to reduce their deployed strategic warheads to 1,550 by 2018, the number set in the New START treaty that the Senate ratified in December 2010.