In a rare step of assembling at their desks on the Senate floor for the historic occasion, senators voted to confirm Sotomayor as the 111th justice and third woman to serve on the high court.
Democratic senators praised Sotomayor as a mainstream moderate while Republicans said she'd bring personal bias and a liberal agenda to the bench in a final day of debate over her nomination.
On Thursday, 59 Democrats voted for Sotomayor while 31 Republicans voted against her. The nine Senate Republicans who voted to confirm her were Sens. George Voinovich of Ohio, Judd Gregg of New Hampshire, Kit Bond of Missouri, Lindsey Graham of South Carolina, Susan Collins of Maine, Olympia Snowe of Maine, Mel Martinez of Florida, Richard Lugar of Indiana and Lamar Alexander of Tennessee.
The vote fell between the last two votes for the two Supreme Court justices nominated by former President George W. Bush. Chief Justice John Roberts earned 78 votes in his confirmation while Samuel Alito garnered 58 votes.
Sotomayor will be sworn in Saturday at the U.S. Supreme Court. Roberts will first administer the constitutional oath in a private ceremony in the Justices' conference room attended by members of Sotomayor's family. Roberts will then administer the judicial oath.
President Obama praised the vote Thursday, saying he is "deeply gratified" by the confirmation.
"With this historic vote, the Senate has affirmed that Justice Sotomayor has the intellect, the temperament, the history, the integrity and the independence of mind to ably serve on our nation's highest court," Obama told reporters.
Sotomayor watched the vote unfold on television among scores of friends and colleagues in a conference room on the 8th floor of the courthouse.
The 55-year-old judge will replace retiring Justice David Souter, a liberal jurist. She is not expected to alter the court's ideological split.
The GOP has decried Obama's call for "empathy" in a justice, painting Sotomayor as the embodiment of an inappropriate standard that would let a judge bring her personal whims and prejudices to the bench.
Her writings and speeches "reflect a belief not just that impartiality is not possible, but that it's not even worth the effort," said Sen. Mitch McConnell, R-Ky., the minority leader. "In Judge Sotomayor's court, groups that didn't make the cut of preferred groups often found that they ended up on the short end of the empathy standard."
But Sotomayor picked up some GOP support even though more than three-quarters of the Senate's 40 Republicans voted against her.
"Judge Sotomayor's decisions, while not always the decision I would render, are not outside the legal mainstream and do not indicate an obvious desire to legislate from the bench," Republican Sen. George Voinovich of Ohio said on the Senate floor Thursday.
"I have confidence that the parties who appear before her will encounter a judge who is committed to recognizing and suppressing any personal bias she may have to reach a decision that is dictated by the rule of law," he said.
Democrats warned Republicans that they risk a backlash from Hispanic voters -- a growing part of the electorate -- if they oppose her.
"Judge Sotomayor should not be chosen to serve on the court because of her Hispanic heritage, but those who oppose her for fear of her unique life experience do no justice to her or our nation. Their names will be listed in our nation's annals of elected officials one step behind America's historic march forward," said Sen. Dick Durbin of Illinois, the No. 2 Democrat.
Republicans bristled at the suggestion that they were not willing to confirm a qualified Hispanic, noting that Democrats used extraordinary measures several years ago to block the confirmation of GOP-nominated Miguel Estrada, a Honduran-born attorney, to a federal appeals court.
GOP senators have said instead that their opposition to Sotomayor is based on her speeches and record, pointing to a few rulings in which they argue she showed disregard for gun rights, property rights and job discrimination claims by white employees. They also cited comments she's made about the role that a judge's background and perspective can play, especially a 2001 speech in which she said she hoped a "wise Latina" would usually make better decisions than a white man.
"I feel very badly that I have to vote negatively -- it's not what I wanted to do when this process started -- but I believe that I'm doing the honorable and right thing," said Sen. Orrin Hatch, R-Utah prior to Thursday's vote.
Republicans have been particularly critical of Sotomayor's position on the Second Amendment right to keep and bear arms. She was part of a panel that ruled this year that the amendment doesn't limit state actions -- only federal ones -- in keeping with previous Supreme Court precedent.
But gun rights supporters said her court shouldn't have called the issue "settled law," and they criticized her for refusing during her confirmation hearings to go beyond what the high court has said and declare that the Second Amendment applies to the states.
The Associated Press contributed to this report.