The Senate passed the bipartisan gun safety bill by a vote of 65-33 late Thursday night.
Fifteen Republicans voted with all Democrats in the chamber to pass the bill. Republican Leader Mitch McConnell supported the final passage, as he was expected to.
The Republicans who supported the measure were Sens. Richard Burr, Roy Blunt, Shelley Moore Capito, Bill Cassidy, Susan Collins, John Cornyn, Joni Ernst, Lindsey Graham, Mitch McConnell, Lisa Murkowski, Rob Portman, Mitt Romney, Thom Tillis, Pat Toomey and Todd Young.
The package is the first major piece of federal gun reform in almost 30 years.
"Tonight, after 28 years of inaction, bipartisan members of Congress came together to heed the call of families across the country and passed legislation to address the scourge of gun violence in our communities," President Joe Biden said in a statement following the bill's passage. "Families in Uvalde and Buffalo -- and too many tragic shootings before -- have demanded action. And tonight, we acted."
"This bipartisan legislation will help protect Americans. Kids in schools and communities will be safer because of it. The House of Representatives should promptly vote on this bipartisan bill and send it to my desk," Biden added.
The House will need to pass the measure before it can be signed into law, and it could take up the bill as early as Friday.
Speaker Nancy Pelosi, D-Calif., promised to "swiftly" bring the gun safety package to the floor once it passes the Senate, "so that we can send it to President Biden's desk."
The Senate had voted earlier Thursday to cut off debate on the bill, which was crafted amid a disturbing uptick in shootings across the U.S. The same 15 Republicans had sided with all 50 members of the Democratic caucus to clear the procedural hurdle.
Senate rules generally require 30 additional hours of debate after the cloture vote, but Majority Leader Chuck Schumer said he wanted to get unanimous agreement to dismiss that requirement and hold a final vote on Thursday.
On Wednesday, House Republicans had encouraged members to vote against the gun safety package.
"The bill throws emergency supplemental federal spending at states to encourage implementation of red flag laws and dramatically increases funding for numerous other grant programs, but the bill's vague language contains insufficient guardrails to ensure that the money is actually going towards keeping guns out of the hands of criminals or preventing mass violence," House Republican Whip Steve Scalise's office wrote in a memo to Republican lawmakers obtained by ABC News.
Key aspects of the legislation include expanded federal background checks for buyers under the age of 21, financial incentives for states to pass "red flag" laws and other intervention programs and closing the so-called "boyfriend loophole."
The bill comes with a $13.2 billion price tag, the nonpartisan Congressional Budget Office announced on Wednesday. According to the office, the bill will be fully paid for by once again delaying a Trump-era ban on prescription drug rebates in Medicare.
Both Schumer and Senate Minority Leader McConnell, R-Ky., backed the legislation -- which was hammered out by a bipartisan group of lawmakers in the weeks after the tragic shooting at an elementary school in Uvalde, Texas.
"This bipartisan gun-safety legislation is progress and will save lives," Schumer said earlier this week. "While it is not everything we want, this legislation is urgently needed."
The Senate's passage of the gun safety bill comes the same day the Supreme Court struck down a New York law regulating concealed handguns in public that mandated residents demonstrate a specific need to carry a handgun outside of the home.
ABC News' Benjamin Siegel contributed to this report.