Senator Mitch McConnell, the Republican leader, leaving the floor on Thursday after his party blocked Mr. Liu's nomination.
The 52-to-43 vote left the Senate 8 votes short of the 60 needed to end debate on the nomination of Goodwin Liu, a Berkeley law professor. Mr. Liu had come under fire from Republicans for tough comments he made in opposition to the nomination of Samuel A. Alito Jr. to the Supreme Court. They also portrayed his legal philosophy as extreme and activist.
The vote came almost exactly six years after a bipartisan group of senators struck an agreement to oppose filibusters against judicial nominees except in extraordinary cases. They acted to head off a threat to change Senate rules to ban such filibusters, a change that was being pushed by Republicans who were then in the majority and were frustrated by Democratic opposition to Bush administration court picks.
Democrats lauded Mr. Liu's credentials and accused Republicans of blocking his confirmation for ideological and political reasons. Republicans said his writings and testimony showed him to be out of the mainstream.
"This nominee, I believe, represents an extraordinary circumstance," said Senator Jeff Sessions, Republican of Alabama. "His record reveals that he believes the Constitution is a fluid, evolving document with no fixed meaning."
On the vote, 49 Democrats, two independents and one Republican, Senator Lisa Murkowski of Alaska, voted to end the filibuster; 42 Republicans and one Democrat, Senator Ben Nelson of Nebraska, voted against allowing a final up-or-down vote on confirmation.
Mr. Liu, 40, was first nominated in February 2010 to the United States Court of Appeals for the Ninth Circuit, which is based in San Francisco.
Coming just weeks after Republicans tried but failed to thwart the confirmation of a district court judge, the Liu vote suggests a new Republican willingness to blockade judicial nominees. It also indicates that President Obama could face serious resistance as he tries to fill vacancies on the bench.
Senator Richard J. Durbin of Illinois, the No. 2 Senate Democrat, said Republicans were adhering to a strategy of trying to keep major judicial vacancies open as long as possible in the hope that a Republican president would be able to fill them after the 2012 elections.
Mr. Durbin said the appeals courts were a particular target "because of the tremendous responsibility and opportunity there is for important and historic decisions - and so Professor Liu has been caught in this maelstrom."
Democrats pointed to strong endorsements of Mr. Liu from the American Bar Association and from noted legal conservatives, accusing Republicans of keeping a highly qualified man off the bench without justification.
Senator Barbara Boxer, Democrat of California, praised Mr. Liu as an "extraordinary American" and warned Republicans that Democrats would not forget how he was treated.
"This is not going to go down easily," said Mrs. Boxer. "I think the ramifications of this filibuster are going to be long and difficult for those who caused this good man to be filibustered."
The tenor of the judicial fight was reminiscent of the mid-2000s, when Republicans and Democrats engaged in a partisan struggle over federal court nominations before striking the bargain that allowed many nominees to clear such procedural hurdles.
But Republicans said they were drawing the line at Mr. Liu. Several of them highlighted what they called his "scathing" testimony against Mr. Alito before the Judiciary Committee in 2006, when he picked apart the nominee's record and said he was too deferential to government power.
"Judge Alito's record," Mr. Liu said in his testimony, "envisions an America where police may shoot and kill an unarmed boy to stop him from running away with a stolen purse; where federal agents may point guns at ordinary citizens during a raid, even after no sign of resistance."
Though Mr. Liu later apologized, Republicans called the marks intemperate and said they showed that the nominee did not have sufficient judicial reserve.
"These statements about Judge Alito and the decisions he's rendered and his philosophy are designed to basically say that people who have the philosophy of Judge Alito are uncaring, hateful and really should be despised," said Senator Lindsey Graham, Republican of South Carolina and one of the architects of the 2005 judicial compromise. "That is a bridge too far, because I share Judge Alito's philosophy."
Republicans raised other objections as well, including a lack of judicial experience. Democrats called Mr. Liu a superb nominee who would also add racial diversity to the bench.
"There is no Asian-American member on the Ninth Circuit Court of Appeals," said Senator Richard Blumenthal, Democrat of Connecticut. "There should be, and Professor Liu ought to be that judge."
For some Senate Republicans, it was the first time they had voted to filibuster a judicial nominee. Only Ms. Murkowski sided with the Democrats.
"I stated during the Bush administration," she said, "that judicial nominations deserved an up or down vote except in 'extraordinary circumstances' and my position has not changed simply because there is a different president making the nominations."