Vice President Joe Biden announces the passage of the Comprehensive Immigration Reform Bill in the Senate.

In a bipartisan vote, the Senate on Thursday passed a sweeping, historic overhaul of the nation’s immigration system – the first attempt to tackle such reform in six years. But the bill appears to face a procedural brick wall in the GOP-led House, with Republican leaders vowing instead to move forward on their own measures.

Fourteen Republicans joined with all Democrats to back the legislation, which would revamp the nation’s legal immigration system, send unprecedented resources to the nation’s southern border, and offer millions of undocumented immigrants a path to legal status and eventual citizenship.

The final vote was 68-32.

To mark the history of the occasion, Vice President Joe Biden presided over the vote and Senate Majority Leader Harry Reid directed senators to vote from their seats in the chamber.

The gallery above the chamber was crowded with tourists, DREAM Act proponents, self-described undocumented immigrants, and members of the media. After the vote tally was announced, a young spectator shouted "Yes we can!" This came even as Biden urged those in attendance to refrain from voicing reaction.

The bipartisan drafters of the legislation, which was first formally unveiled in April, came one by one to the Senate floor Thursday afternoon to make deeply personal appeals for the passage of a bill they described as a compassionate, economically sound measure necessary to maintain the American Dream central to the nation’s identity.

Sen. Marco Rubio delivers remarks before Thursday's vote on sweeping immigration reform legislation.

“Even with all our challenges, we remain the shining City on the Hill. We are still the hope of the world,” said Sen. Marco Rubio, a Florida conservative and Cuban-American whose support of the legislation was key to wooing Republican support. “Go to our factories and fields. Go to our kitchens and construction sites. Go to the cafeteria of this very Capitol. There, you will find that the miracle of America still lives.”

“Pass this bill and keep the American covenant alive,” urged Sen. Chuck Schumer, the top Democrat on the bipartisan “Gang of Eight” that first unveiled compromise legislation in April.

In emotional remarks right before the vote, Reid invoked the late Sen. Ted Kennedy, who led the failed effort six years ago to pass a comprehensive immigration reform bill.

“Sen. Kennedy knew the day would come when a group of senators divided by party, but united by love of country, would see this fight to the finish,” he said. “That day is today.”

In the face of great fanfare and emotion on Thursday, the bill remains many hard-fought steps from the president's desk, and the victory for backers of the reform may ultimately be short-lived.

Despite bipartisan support in the Senate, the immigration legislation faces a rocky path in the GOP-controlled House, where opposition to the citizenship provision is significantly stronger. Boehner has pledged not to bring the Senate bill up for a vote, pointing instead to smaller pieces of immigration legislation focused on border security and enforcement. On Thursday, he reiterated that he will not bring legislation to the House floor that does not have majority support from the Republican conference, and he extended that pledge even to merged legislation that could blend House- and Senate-passed bills.

In a statement lauding the Senate's passage of the bill, President Barack Obama urged the diverse coalition of groups that worked for reform to keep up the fight as the House turns its attention to the immigration issue.

"Now is the time when opponents will try their hardest to pull this bipartisan effort apart so they can stop commonsense reform from becoming a reality," he said. "We cannot let that happen."

"Today, the Senate did its job, he said. "It’s now up to the House to do the same."

Despite the difficult road ahead, the Senate's passage of the bill represents the furthest legislative progress on a comprehensive immigration bill since 2006. That effort passed the upper chamber but languished without support from the House. Another attempt in 2007 fell well short of the 60 votes needed to advance the legislation in the Senate.

J. Scott Applewhite / AP Senate Foreign Relations Committee Chairman Sen. Robert Menendez, D-N.J. leaves the Senate floor on Capitol Hill in Washington, Thursday, June 27, 2013, prior to the final vote on the immigration reform bill.

The home stretch for the months-long Senate process to pass the bill comes after a last-minute deal to add a massive influx of funding and resources for the U.S.-Mexico border, doubling the number of border security agents on patrol and requiring the completion of 700 miles of fencing. That compromise – labeled “almost overkill” by cosponsor Republican Sen. Bob Corker of Tennessee – was designed to recruit more Republicans to push the legislation over the finish line.

Opponents of the border “surge” drafted by Corker and Republican John Hoeven of North Dakota say there’s no guarantee that the legislation’s border security goals will be met before undocumented workers are eligible to apply for green cards.

The legislation's foes also contend that the citizenship proposal amounts to "amnesty" that rewards lawbreakers without sufficient protections against new waves of illegal immigration.

“The amnesty will occur, but the enforcement is not going to occur, and the policies for future immigration are not serving the national interest,” said Sen. Jeff Sessions of Alabama, one of the most vocal opponents of the bill. “I urge my colleagues to vote no.”

NBC's Kelly O'Donnell and Frank Thorp contributed to this report.