She was confirmed Wednesday by a vote of 85-13.
Rice, 50, replaces Colin Powell and becomes the first black woman to serve as America's top diplomat.
Plans were made for her to be sworn in at the White House Wednesday night, take her place in the State Department Thursday morning and have a more elaborate swearing-in by the president at the agency on Friday.
Twelve Democrats and independent James Jeffords of Vermont voted against Rice. The Democrats included high-profile Senate members such as Edward M. Kennedy and John Kerry, both of Massachusetts.
President Bush praised Rice at ashortly before the Senate vote on her confirmation. "She is going to make a wonderful secretary of state," he said.
In other Cabinet news, the Senate confirmed Jim Nicholson to be the new secretary of Veterans Affairs and Mike Leavitt to be the new secretary of Health and Human Services.
Also Wednesday, the Senate Judiciary Committee advanced Alberto Gonzales' nomination as attorney general to the full Senate on a 10-8 party line vote.
For Rice, what had seemed at the outset to be an easy road to confirmation turned into a sometimes angry debate over Mr. Bush's Iraq policies and her role in making the case for going to war.
Democrats said mistakes by the administration had led to mounting American casualties. As the debate drew to a close, word came from Iraq of the crash of a U.S. military transport helicopter in bad weather, killing at least 30 people in the worst U.S. loss since the war.
Kennedy charged that Rice, as Mr. Bush's national security adviser, provided Congress with "false reasons" for going to war. Had she not, Kennedy said, "It might have changed the course of history."
By contrast Republicans praised Rice during Tuesday's lengthy debate as a distinguished academic and public servant who tells the truth.
"She's always been candid and honest, and she listened," Sen. Chuck Hagel, R-Neb., said.
Rice's nomination was never in doubt, however. Republicans had hoped to hold the vote last week, on the same day that Mr. Bush took the oath for his second term, but Democrats asked for more time. The GOP accused Democrats of inappropriately delaying Rice's confirmation to make political statements about Iraq policy.
Although she was assured of confirmation, Rice got the most "no" votes since World War II. Seven senators voted against Henry Kissinger and six each against Dean Acheson and Alexander Haig.
On the Senate floor Wednesday, Sen. John McCain, R-Ariz., suggested Democrats are sore losers. Rice had enough votes to win confirmation, as even her Democratic critics acknowledge, McCain said.
"So I wonder why we are starting this new Congress with a protracted debate about a foregone conclusion," McCain said. Since Rice is qualified for the job, he said, "I can only conclude that we are doing this for no other reason than because of lingering bitterness over the outcome of the election."
An academic who specialized in the study of the now-defunct Soviet Union, Rice has been one of Mr. Bush's closest advisers as his national security adviser for four years. In testimony last week to the Senate Foreign Relations Committee, she swore she has not been shy about disagreeing with him privately at times.
Now, she will be at his side trying to improve relations with European allies, pursuing a Middle East settlement between Israel and the Palestinians, seeking a way to stop North Korea and Iran from developing nuclear weapons — and, above all, trying to pacify Iraq with limited additional U.S. casualties.
Rice was born in Birmingham, Ala. She earned a bachelor's degree in political science from the University of Denver, a master's from Notre Dame and a doctorate from the Denver's Graduate School of International Studies.
The 85-13 roll call by which the Senate voted to confirm the nomination of Condoleezza Rice as secretary of state.
On this vote, a "yes" vote was a vote to confirm and a "no" vote was a vote not to confirm.
Voting "yes" were 32 Democrats and 53 Republicans.
Voting "no" were 12 Democrats and one independent.
Baucus, Mont.; Biden, Del.; Bingaman, N.M.; Cantwell, Wash.; Carper, Del.; Clinton, N.Y.; Conrad, N.D.; Corzine, N.J.; Dodd, Conn.; Dorgan, N.D.; Feingold, Wis.; Feinstein, Calif.; Inouye, Hawaii; Johnson, S.D.; Kohl, Wis.; Landrieu, La.; Leahy, Vt.; Lieberman, Conn.; Lincoln, Ark.; Mikulski, Md.; Murray, Wash.; Nelson, Fla.; Nelson, Neb.; Obama, Ill.; Pryor, Ark.; Reid, Nev.; Rockefeller, W.Va.; Salazar, Colo.; Sarbanes, Md.; Schumer, N.Y.; Stabenow, Mich.; Wyden, Ore.
Akaka, Hawaii; Bayh, Ind.; Boxer, Calif.; Byrd, W.Va.; Dayton, Minn.; Durbin, Ill.; Harkin, Iowa; Kennedy, Mass.; Kerry, Mass.; Lautenberg, N.J.; Levin, Mich.; Reed, R.I.
Alexander, Tenn.; Allard, Colo.; Allen, Va.; Bennett, Utah; Bond, Mo.; Brownback, Kan.; Bunning, Ky.; Burr, N.C.; Chafee, R.I.; Chambliss, Ga.; Coburn, Okla.; Cochran, Miss.; Coleman, Minn.; Collins, Maine; Cornyn, Texas; Craig, Idaho; Crapo, Idaho; DeMint, S.C.; DeWine, Ohio; Dole, N.C.; Domenici, N.M.; Ensign, Nev.; Enzi, Wyo.; Frist, Tenn.; Graham, S.C.; Grassley, Iowa; Hagel, Neb.; Hatch, Utah; Hutchison, Texas; Inhofe, Okla.; Isakson, Ga.; Kyl, Ariz.; Lott, Miss.; Lugar, Ind.; Martinez, Fla.; McCain, Ariz.; McConnell, Ky.; Murkowski, Alaska; Roberts, Kan.; Santorum, Pa.; Sessions, Ala.; Shelby, Ala.; Smith, Ore.; Snowe, Maine; Specter, Pa.; Stevens, Alaska; Sununu, N.H.; Talent, Mo.; Thomas, Wyo.; Thune, S.D.; Vitter, La.; Voinovich, Ohio; Warner, Va.
Republicans Not Voting=
Burns, Mont.; Gregg, N.H.