In a politically divided town where compromise can be fleeting and partisanship is the norm, the Republican senator from South Carolina has become a leading voice on nearly every major issue before Congress this year - partly because he has not always followed his party's official stances.
Graham, a conservative who has never been afraid to buck his party and work with Democrats, is one of four Republicans in the "Gang of Eight" group of senators who are trying to craft a deal to revamp the nation's immigration system.
It is an effort that has caused some grumbling in Graham's conservative home state. And it has angered conservative Republicans who vehemently oppose finding ways to provide legal status for most of the estimated 11 million illegal immigrants in the United States.
Graham, 57, also deviated from the party line this week over looming across-the-board spending cuts, saying he would consider raising up to $600 billion in new tax revenue if Democrats accepted significant changes to the Medicare and Medicaid health programs as part of a broader, long-term budget deal.
By suggesting this week that he would be willing to consider more tax increases beyond those that Congress approved on the wealthiest Americans in January, Graham stood virtually alone in his party.
The depth of some Republicans' objections to more tax increases was evident when Republican Senator Ron Johnson of Wisconsin speculated that House of Representatives Speaker John Boehner "would lose his speakership" if he backed such a plan.
At the same time, Graham has delighted some conservatives by joining his close friend, Arizona Senator John McCain, in spearheading criticism of President Barack Obama's administration for its handling of the fatal attack on the U.S. diplomatic compound in Benghazi, Libya, last September 11.
Graham and McCain have cast the attack, which killed U.S. Ambassador Christopher Stevens and three other Americans, as a security failure. They used the episode to delay the Senate confirmation of Chuck Hagel, a former Republican senator from Nebraska, as Obama's defense secretary.
That effort came to an end on Tuesday, when the Senate voted 58-41 to confirm Hagel. Graham voted against Hagel's confirmation.
"I hope he can exceed expectations," Graham told reporters on Tuesday. "I don't dislike Chuck Hagel. I just don't think he's the best guy."
His positions on immigration, government spending and Hagel have amounted to a dizzying series of political twists for Graham as the two-term senator prepares for a re-election campaign next year - and a possible challenge from the conservative Tea Party movement.
"From a political standpoint, Graham has been going left and right at the same time," said William Galston, a senior fellow at the Brookings Institution who was a policy adviser to former President Bill Clinton.
"He is sticking his neck out. South Carolina politics can be pretty unforgiving," Galston said. "But knowing him a little bit, I think he's doing what he believes in both cases. He is serious about policy and governance."
'GOOD CHANCE' FOR IMMIGRATION BILL
Graham and McCain met with Obama at the White House on Tuesday to press their views on immigration and the $85 billion in mandatory spending cuts that are scheduled to take effect at the end of the week.
Obama had called Graham, McCain and another Republican in the Senate group discussing immigration, Florida Senator Marco Rubio, last week.
Graham has been criticized on the immigration issue in a South Carolina radio ad by Numbers USA, a group that supports lower levels of immigration.
The ad, which will begin airing statewide on Wednesday, calls Graham's immigration plan "amnesty and welfare" for illegal immigrants.
"Who elected Lindsey Graham to demand millions more immigrant workers when so many South Carolinians are jobless?" the ad says.
But immigration has become a more pressing political priority for Republicans after Obama crushed Republican presidential candidate Mitt Romney among the nation's fast-growing Hispanic population in the November election.
Graham, who worked on a failed immigration overhaul in 2007, said after the White House meeting with Obama he believed there was "a good chance" of passing a comprehensive immigration bill this year.
"The president is very sincere, wanting a bill and wants to know what he can do to help," Graham said.
Graham is the only member of the Senate "Gang of Eight" who is up for re-election next year, but Galston said he is not running to the right to prevent a primary challenge like many of his Republican colleagues have.
"I have to believe that he figures he has enough support to withstand the inevitable criticisms from the right. He has been in South Carolina politics long enough to know what to expect," Galston said.
Still, like his friend McCain, Graham sometimes cannot help taking a few potshots at his fellow Republicans.
On CNN on Monday, he observed that Republicans would be happy to attack Obama's response to the looming spending cuts, even though they do not have their own plan.
"Both parties need to grow up," Graham said.
At the Capitol on Tuesday, Graham told reporters there had been no response to his comments about potential revenue savings in a budget deal.
Republican leaders in both the House and the Senate so far have ruled out raising new revenue by plugging tax loopholes in a budget deal, and most Democrats have been unenthusiastic about including changes to federally funded social benefit programs, known in Washington parlance as "entitlements."
"I hope somebody over there is listening. It really is the chance to do something big," Graham said. "If you bend the curve on entitlements, I'm willing to do revenue."
(Editing by David Lindsey and Christopher Wilson)