The Senate overwhelmingly approved Sen. John F. Kerry (D-Mass.) as the next secretary of state Tuesday afternoon, with three Republican “no” votes.

The vote was 94 to 3, clearing the way for Kerry to formally take over from Secretary of State Hillary Rodham Clinton on Friday.

He assumes the post amid a civil war in Syria that has killed an estimated 60,000 people, stalled nuclear negotiations with Iran and the spread of militancy across North Africa. U.S. relations with Russia are at a low point, the United States is struggling to manage a changing relationship with a rising China and the prospects for new Middle East peace efforts appear dim.

Three Republicans voted against Kerry: Sens. Ted Cruz and John Cornyn of Texas, and Sen. James M. Inhofe (Okla).

Inhofe said voting against Kerry, whom he called a “good friend,” was a no-brainer.

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“We joke around a lot,” the Republican lawmaker said in a phone interview Tuesday afternoon. “But I told him I never agreed with him on anything, going all the way back to the Sandinistas.”

Inhofe said that he was concerned in particular that Kerry appears to make global warming a centerpiece issue and that Kerry has been too deferential to global organizations such as the United Nations.

Kerry, 69, was the failed 2004 Democratic candidate for president, but the State Department job represents a long-held ambition for the foreign policy expert. He will become the 68th top U.S. diplomat and the first white man to hold the post since Warren Christopher in 1997.

“His whole life has prepared him for this job,” Sen. Richard Blumenthal (D-Conn.) said on the Senate floor.

Kerry became a trusted diplomatic envoy for President Obama during Obama’s first term, negotiating with Pakistan on behalf of the administration and carrying blunt messages to Afghan President Hamid Karzai. He is expected to continue his focus on Afghanistan and Pakistan as secretary, and he pledged last week to renew U.S. efforts toward a Middle East peace settlement.

Earlier Tuesday, the Senate Foreign Relations Committee approved Kerry’s nomination by a voice vote. There was no opposition. The five-term Massachusetts Democrat has led the Foreign Relations Committee for the past four years.

The committee approved a glowing commendation of Kerry, listing among his qualifications that he is “the keeper of the Senate’s conscience on global climate change.”

Kerry arrived about halfway through the Senate vote, walking onto the chamber’s floor with Sen. Lindsey O. Graham (R-S.C.). Kerry abstained but watched the vote from the front of the chamber, standing with Sen. Mark Kirk (R-Ill.) and accepting congratulations from his colleagues. He briefly stepped into the Senate Cloak Room before emerging in time to hear the final count. People seated in the upper Senate gallery and senators on the floor, including Sen. Elizabeth Warren (D-Mass.), broke into applause when the final count was read. Kerry thanked them by bowing slightly and smiling.

As the Senate proceeded to other business, Sen. Charles E. Schumer (D-N.Y.) told the chamber: “I think for John Kerry, the best is yet to come.”

Kerry, who will resign his Senate seat to take the Cabinet post, took a victory lap on the Senate floor, shaking hands with colleagues as the vote neared an end. He is expected to make his departing speech on the floor Wednesday.

Staff writer Ed O’Keefe contributed to this report.