Vice President Mike Pence presided over the roll call, his potential tie-breaking vote unnecessary.
The confirmation will mark a major victory for President Donald Trump, who will soon be able to take credit for appointing two conservative justices to the Supreme Court during his relatively brief time in office so far and possibly create a conservative majority on the bench for a generation.
Speaking to reporters aboard Air Force One while flying to a campaign rally in Kansas, Trump said of Kavanaugh: "We're very honoured that he was able to withstand this disgusting, terrible attack by the Democrats".
The New York Democrat also blasted the "biased, unfair" confirmation process and urged Americans to vote.
By Friday afternoon, the sole remaining undeclared senator was Joe Manchin, a West Virginia Democrat. Every voting Republican backed the 53-year-old conservative judge. Lisa Murkowski of Alaska was the only Republican who did not vote to confirm; rather than a "no" vote, she voted "present". Murkowski had already announced her intention to vote "no".
Senate leader Mitch McConnell said: "The court guards our right and the Senate guards the court".
Trump watched the confirmation vote on a large-screen television tuned to Fox News in a wood-paneled cabin on the plane.
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Kavanaugh's nomination seals a conservative majority on the nine-seat high court, possibly for decades to come.
All the while, crowds of demonstrators - mostly Kavanaugh opponents - ricocheted around the Capitol's grounds and hallways, raising tensions, chanting slogans, interrupting lawmakers' debates, confronting senators and often getting arrested. "Big day for America!" he tweeted.
Trump, seeking a legacy as the president who put a strongly conservative stamp on the court, said on Saturday before the vote that Kavanaugh would do "great, great" job there.
Democrats furiously accused the GOP of short-circuiting efforts to examine the allegations and of rushing the nomination through, and of ignoring the changed political dynamics surrounding complains of misconduct against powerful men ushered in by the #MeToo movement.
Hundreds of protesters against Kavanaugh had gathered on Saturday on the grounds of the Capitol and at the Supreme Court.
After roughly an hour, Trump grew looser, riffing on the North Korea talks, the move of the USA embassy to Jerusalem, Kanye West and the National Football League.
He said: "I stand before you today on the heels of a tremendous victory for our nation". Notably, neither Ford nor Kavanaugh spoke with the Bureau for the probe. Lindsey O. Graham (R-S.C.), who gave a fiery defense of the nominee during the September 27 hearing, "and, at least on our side, for wanting to win too much".
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All proceeds gathered at Tough Enough to Wear Pink will be donated to the American Cancer Society for its breast cancer programs. Bush said football coaches and players, cheer and pom will all sport pink to call attention to the threat of breast cancer.
"We must always remember that it is when passions are most inflamed that fairness is most in jeopardy", said Collins, perhaps the chamber's most moderate Republican. Manchin, the only Democrat supporting Kavanaugh, faces a competitive re-election race next month in a state Trump carried in 2016 by 42 percentage points.
Manchin expressed empathy for sexual assault victims.
President Donald Trump celebrated the confirmation of Brett Kavanaugh to the Supreme Court at a rally in Kansas on Saturday, condemning Democrats for what he called a "shameless campaign of political and personal destruction" against Kavanaugh.
The Senate backed Brett Kavanaugh's nomination by 50 votes to 48.
But the report from the Federal Bureau of Investigation was met with mixed response, with survivors and Democrats saying it was "insufficient", but Mr Trump and Republicans calling it "thorough" and "professional".
"Very, very good", Trump said.
Trump was aboard Air Force One, travelling to a campaign rally in Kansas, as the Senate voted on an extraordinarily fraught nomination that sparked angry protests, nail-biting votes and a national reckoning about sexual assault allegations and who should be believed.
Like other Republicans, he sees Kavanaugh as a justice who would sweeten the chances of reversing Roe v. Wade, the 1973 Supreme Court decision that affirmed women's constitutional right to legal abortion.
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It is wrong, they haven't been recognised, Prashant Bhushan replied, saying it was the responsibility of the court. To which the CJI remarked, "You need not remind us what's our responsibility", before dismissing the petition.