Several Republicans, including several congressmen, are eyeing the seat. The more crowded the field, the more likely the GOP race will pit mainstream conservatives against the hardliners who had grown disenchanted with Chambliss for working with Democrats to find common ground on budget and tax issues.
Democrats, meanwhile, hope for exactly that kind of Republican fracas. They view the 69-year-old Chambliss' decision as an opportunity to reverse the GOP's total domination in a state that once elected moderate Democratic governors such as Jimmy Carter.
"Regardless of what happens, it's going to be a 10-person race," said 11-term U.S. Rep. Jack Kingston of Augusta, who is now considering a bid. "I think you'll probably have a self-funder in there, and you can have a mad scramble."
Among Kingston's colleagues, other possible candidates include U.S. Reps. Paul Broun, Phil Gingrey and Tom Price. Former Gov. Sonny Perdue and former Secretary of State Karen Handel are also viewed as potential contenders.
"There's a lot of math going on today," said Bert Brantley, a Republican strategist and former Perdue aide. "It's a lot of phone calls with donors and strategists as people ask themselves, 'Can I make this work financially? Electorally?'"
Democrats declared Georgia as a prime target. U.S. Rep. John Barrow and Atlanta Mayor Kasim Reed are the most obvious choices for a state party with an otherwise thin bench.
"There are already several reports of the potential for a divisive primary that will push Republicans to the extreme right," said Guy Cecil, executive director of the Democratic Senatorial Campaign Committee. "Regardless, there's no question that the demographics of the state have changed, and Democrats are gaining strength. This will be a top priority."
Democrats' optimism runs in the face of recent trends. President Barack Obama ran stronger here than in other Deep South states, but still lost by 8 percentage points in 2012. But Republicans over the last decade have amassed near super-majorities in the legislature and now control every statewide elective office and most of the Peach State's congressional seats.
Chambliss was first elected to Congress in the 1994 Republican wave. He moved up to the U.S. Senate after defeating Democratic incumbent Max Cleland, a triple amputee from his Vietnam war service, in 2002. Chambliss was widely criticized for slashing campaign ads that featured Osama bin Laden and Saddam Hussein and that criticized Cleland as weak on defense and homeland security issues.
Chambliss revealed his decision not to seek re-election in a written statement Friday morning.
The senator drew the ire of hard-line conservatives over his participation in the "Gang of Six," a group of three Democrats and three Republicans that tried but failed to fashion a grand compromise on fiscal issues. One of those senators, Democrat Mark Warner of Virginia, praised Chambliss as a statesman on Friday.
Conservative angst resurfaced when Chambliss voted for the tax-and-debt compromise that Obama fashioned with congressional leaders over the New Year's holidays to avoid the fiscal cliff. The measure held taxes steady for the middle class but allowed them to rise at incomes over $400,000 for individuals and $450,000 for couples.
Broun and Price had already floated the possibility of challenging Chambliss in a GOP primary.
"I have no doubt that had I decided to be a candidate, I would have won re-election," Chambliss said in his statement. "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."
National tea party leader and Georgia resident Amy Kremer celebrated Chambliss's departure. "Many people in the tea party movement here in Georgia felt Chambliss was tired and unwilling to fight the difficult battles to control government spending in Washington without increasing our nation's tax burden," she said.
Several Republicans acknowledged the potential of a divisive fight pitting tea party-aligned candidates—someone like Broun or Gingrey—against more establishment conservatives, like Kingston. Several Republicans said Price could appeal to both camps.
A Price spokeswoman said her boss "is speaking with a number of folks ... and listening to their observations and advice." Gingrey focused his remarks Friday on Chambliss. Broun's office did not respond to a request for comment.
A Handel spokesman declined comment. With the backing of Sarah Palin, Handel proved a formidable statewide candidate in her 2010 bid for governor, narrowly losing a Republican primary runoff to eventual winner Nathan Deal, a former congressman. A Deal spokesman said he plans to seek re-election in 2014.
Brantley, the Perdue confidant, said he had not talked with his former boss Friday about the race.
Republicans said Friday that the potential candidates will spend the next few weeks running a quiet campaign among donors and power players before making a decision.
Georgia Democratic Party Chairman Mike Berlon, meanwhile, said Democrats "want to get the right candidate and line up behind him or her in the next few weeks." Neither Barrow nor Reed tipped their hands.
In 2012, Barrow withstood a Republican redistricting plan to win another term as the last white Democrat representing a Deep South state in the U.S. House. Should he run for the Senate, he'd almost certainly hand the 12th District seat to the GOP.
Barrow benefited last fall from a nasty GOP primary that yielded a conservative candidate with little money, the kind of scenario Democrats would love to see repeated in a Senate race.
Berlon called Atlanta's Reed "a rising star who has the talent to play at the national level." Reed, a prominent campaign surrogate for the White House last fall, appears poised to coast to victory in his mayoral re-election bid this year.
Sen. Johnny Isakson, who will become Georgia's senior senator when Chambliss retires, deferred any talk of 2014. "Saxby has been my friend for 50 years, since we started at the University of Georgia," he said. "I'm going to miss my friend. ... I won't get into predicting elections. I've learned that Georgia voters usually make the right decision, so I'll leave it to them."
Associated Press writer Donna Cassata in Washington, D.C., contributed to this report.
Follow Barrow on Twitter (at)BillBarrowAP.