"We're going to have to start consolidating as Republicans," he said in an exclusive interview with CNN's Kate Bolduan on his decision to leave the 2016 GOP presidential nominating race.
Graham's parting plea echoes what prominent Republicans and conservatives have been saying for months as Trump's dominance and that of other outsiders have left the GOP establishment rattled and split among several candidates.
Conservative Washington Post blogger Jennifer Rubin put it bluntly in a column: "Lindsey Graham is out, others should follow."
Graham is the fourth candidate to drop out so far, but that hasn't yet dented the strong numbers of the anti-establishment figures leading the pack. Stuck in single digits, Graham never caught on even among establishment Republicans, who are mostly split among at least four other candidates, leaving Trump with a commanding lead in national polls.
A December CNN/ORC poll shows insurgent candidates Trump, Texas Sen. Ted Cruz and former neurosurgeon Ben Carson grabbing 66% of the support of Republicans, with the remaining candidates divvying up the rest.
"This is a Mars and Venus thing," said Craig Shirley, a Ronald Reagan biographer. "They don't even speak the same language."
The South Carolina senator has been among Trump's fiercest critics, calling him a "race-baiting, xenophobic, religious bigot" who should "go to hell." But, like Scott Walker, Rick Perry and Bobby Jindal before him, Graham's exit proves that criticizing Trump can earn a candidate temporary notice for a clever soundbite but not much else.
Known for his wit and hawkish approach to foreign policy, Graham sounded the alarm as he folded his hand, laying out the high stakes for the GOP.
"This is an election for the heart and soul of the Republican Party," Graham said on CNN. "This is no longer about 2016. This is about who we are as a party, where do we want to go, where do we take the country."
Indeed, Trump's success has sparked a debate about what it means to be conservative -- yet the party has struggled to find party wise men capable of settling the argument.
The February 20 South Carolina primary will likely provide some clarity as the state has a history of backing the eventual nominee, with 2012 as the outlier.
"We haven't been the wild-haired fanatic that people think we are when it comes to backing candidates," said David Woodard, a political science professor at Clemson University, about South Carolina. "When it comes down to vote, we have been sane and the extreme candidates fade, and I'm expecting that with Trump."
More immediately, Graham's exit could shuffle allegiances in his home state.
"I think the most important consequence is that key South Carolina organizers now have no excuse to sit on the sidelines. Plenty were demurring out of respect to Lindsey and now they can fully engage," said Brad Todd, a GOP consultant who worked for Bobby Jindal's political action committee.
"It's a shame the debate structure never let Lindsey have his real shot," Todd said, referring to the two-tiered debates that relegated Graham, with his low poll numbers, to the undercard event out of the spotlight. "His leadership on foreign policy is critical to the party, and it would've been important in the race."
In South Carolina on Monday, a string of Graham supporters switched to Ohio Gov. John Kasich's team. The most recent Winthrop University poll showed Kasich at 1% support, with Graham at 2%.
Kasich wrote on Twitter: "Enjoyed Senator Graham's wit and respect his seriousness on national security experience matters. Best wishes to him."
But Graham's exit could mean the most for Florida Sen. Marco Rubio and former Florida Gov. Jeb Bush, who poll at 11% and 9% respectively in the state.
"With Graham out, Jeb Bush inherits his support, which means he goes from 3% to 2.8%," quipped Shirley, the Reagan biographer.
Bush, who has adopted Graham's playbook as the anti-Trump, tweeted his support of Graham.
"Nobody is more clear-eyed about ISIS than my friend Lindsey Graham," he wrote. "I hope as he leaves the race our country listens to his counsel."
Bush allies have been running ads in South Carolina since September outlining his record in Florida.
Rubio said that Graham was "a defender of a strong national defense, as I am" and described him as one of the most forceful voices on the military.
Graham said that he isn't likely to endorse soon, and John McCain, his most vocal backer, announced he wouldn't back anyone in the primary.
Graham did name check two of his former opponents, however, when asked whom he trusted to fight for men and women in the military.
"Really, I think Jeb and Marco get it," he said.
Shirley said he didn't think Lindsey Graham's departure from the GOP field would in and of itself have much effect on the race.
But more broadly it represents a trend of concentrating the establishment vote on one side with outsiders on the other likely to pick up steam as the first rounds of voting begin.
"This schism is both old and new to the Republican party. It goes back to Taft and Eisenhower through Goldwater. Reagan consolidated the Republican coalition," Shirley said. "Then George W. Bush and (political adviser Karl) Rove resplit the party by corporatizing it and introducing the concept of big-government Republicanism."
"We're witnessing the death and rebirth of the Republican Party," he said.