Kavanaugh was sworn in a few hours later in a private ceremony that included Kavanaugh's wife, children and parents.
Leading up to the vote and lasting into the evening, hundreds of protesters convened on the Supreme Court steps, shouting, ''We believe survivors."
Protesters crossed police lines, chanting, "November is coming," with some holding signs that read "We believe all survivors." Officers soon began detaining the protesters, whose hands were zip-tied before being led from the building.
Roll call for the vote began around 3:45 p.m. ET and ended shortly after 4 p.m. Protesters disrupted the vote several times, shouting at senators before being escorted away as Vice President Mike Pence, who would cast a "yes" vote if tied, presided.
Sen. Lisa Murkowski of Alaska was the lone Republican to break with her party, saying she was against Kavanaugh's nomination. But she voted "present" out of respect for Sen. Steve Daines, R-Mont., who didn't attend the vote because he was at his daughter's wedding. The "pairing" kept the margin at a razor-thin difference of two.
Two lone holdouts also announced their plans Friday. West Virginia Democrat Joe Manchin broke ranks to vote "yes" Saturday and Maine Republican Susan Collins also voted "yes," affirming her announcement in a 45-minute speech on the Senator floor Friday.
Before the vote, party leaders gave a final plea for their case. Senate Minority leader Charles Schumer urged people to get out and vote in November.
Senate Majority Leader Mitch McConnell said there could not be a more qualified candidate and said the vote will "end this brief, dark chapter in the Senate's history and turn the page to a brighter tomorrow."
Trump tweeted about the victory, applauding the process.
"I applaud and congratulate the U.S. Senate for confirming our GREAT NOMINEE, Judge Brett Kavanaugh, to the United States Supreme Court. Later today, I will sign his Commission of Appointment, and he will be officially sworn in. Very exciting!"
Trump also paused for a statement on his way to a rally in Kansas, telling reporters how happy he is for the historic vote despite the hardship on Kavanaugh leading up to the vote.
"The beautiful thing is he is now in. He's going to be there for a long time," Trump said.
On Friday by a razor-thin margin, the Senate voted mostly down party lines in a 51-49 vote to move forward with a final confirmation vote for Kavanaugh, a move that sparked protests on the steps of the Capitol and across the nation.
The confirmation process stalled in September amid allegations of sexual misconduct against Kavanaugh which resulted the Senate Judiciary Committee hearing testimony from the nominee and Christine Blasey Ford, who alleges Kavanaugh sexually assaulted her when they were in high school.
Kavanaugh denies the allegation, which also prompted an investigation by the FBI limited in scope and time.The Senate agreed to the one-week investigation on the urging of Republican Jeff Flake, who is not seeking re-election this November.
FBI had not found any corroborating witnesses to back Ford's claim. Democrats are complaining the FBI investigation is inconclusive, say they failed to interview key witnesses and urged public release of the report.
Trump, while talking to reporters in Kansas, thanked the FBI for how they handled the investigation.
"They worked hard and fast. The report was detailed and thorough," Trump said. "The extra week delay was a terrific thing for the process."
Earlier Trump tweeted his support for Kavanaugh and praised crowds gathered at the Capitol to support the nominee.
"It is a beautiful thing to see - and they are not paid professional protesters who are handed expensive signs. Big day for America!"
"I think he's highly qualified for the Supreme Court," she said, adding she is glad that Kavanaugh and Ford were heard.
Susan Rice, national security adviser to President Barack Obama, tweeted she would consider challenging Collins in 2020, saying she was deeply disappointed in Collins' vote. Collins has served in the Senate since 1997.