Chambliss -- who defeated incumbent Democratic Sen. Max Cleland in 2002 -- said in a statement announcing his decision he is "proud of my conservative voting record" and was not bowing out of a 2014 race out of concern he might have to face a primary challenge, saying he has "no doubt that had I decided to be a candidate, I would have won re-election."
"Instead, this is about frustration, both at a lack of leadership from the White House and at the dearth of meaningful action from Congress, especially on issues that are the foundation of our nation's economic health," Chambliss said. "The debt-ceiling debacle of 2011 and the recent fiscal-cliff vote showed Congress at its worst and, sadly, I don't see the legislative gridlock and partisan posturing improving anytime soon."
Conservatives have criticized Chambliss, 69, for his role in the so-called Gang of Six -- a bipartisan group of senators who pushed for including higher taxes in addressing the growing federal debt -- Fox News said.
In his 2002 campaign, Chambliss ran a TV ad criticizing Cleland's votes on homeland security measures, while prominently featuring images of al-Qaida leader Osama bin Laden and Iraqi President Saddam Hussein.
Supporters of Cleland -- a triple amputee as a result of a hand grenade explosion during his deployment with the Army in Vietnam -- accused Chambliss of impugning Cleland's patriotism. Chambliss said he "never questioned the patriotism of my opponent," only his voting record.
Rivals in the contest to succeed Chambliss may include Rep. Jack Kingston, R-Ga., an 11-term House veteran, who told Fox he is considering entering the race.
"Regardless of what happens, it's going to be a 10-person race," Kingston said.
Guy Cecil, executive director of the Democratic Senatorial Campaign Committee, said Chambliss' retirement offers Democrats "one of our best pick-up opportunities" of 2014, Fox News reported.