>> Related: How will U.S. Sen. Johnny Isakson's replacement be chosen?

Gov. Brian Kemp, a Republican, will appoint a replacement for Isakson, who was elected to a third term by a wide margin in 2016. Though Isakson’s term doesn’t expire until 2022, the timing of his retirement means the seat will be on the ballot next year.

Three Georgia Democrats have already announced challenges to U.S. Sen. David Perdue, a first-term Republican who is up for election in 2020. Isakson’s seat will likely draw several other Democrats, who see Georgia as increasingly competitive.

It’s not yet clear who Kemp will appoint to fill Isakson’s seat, though potential candidates include Georgia Attorney General Chris Carr, state Senate Pro Tem Butch Miller, Lt. Gov. Geoff Duncan, U.S. Rep. Doug Collins and U.S. Agriculture Secretary Sonny Perdue.

Among the potential Democratic contenders for the seat are the Rev. Raphael Warnock, the pastor of Ebenezer Baptist Church; Jon Ossoff, a former candidate for Georgia’s 6th Congressional District; Jason Carter, the runner-up for governor in 2014; and Michelle Nunn, who was defeated by David Perdue in the 2014 Senate race.

Stacey Abrams, who narrowly lost last year’s race for governor and earlier ruled out a 2020 bid for Perdue’s seat, said through a spokesman that she would not run next year. Instead, she said, she’s focused on an expansion of her voting rights initiative.

“While she will not be a candidate herself, she is committed to helping Democratic candidates win both Senate races next year,” said the spokesman, Seth Bringman.

The vote will be held in November and, instead of featuring party primaries, will rely on the “jungle primary” system that’s likely to force a runoff. The winner of the 2020 race will fill the remaining two years of Isakson’s term and then face a 2022 contest for a full six-year term.

‘Heart and soul’

A four-decade veteran of Georgia politics, Isakson is famed for his work ethic and busy schedule. His aides and allies long dismissed talk that he could step down early, and they even floated the idea of a fourth term at the state GOP convention in May.

But he has grappled with complications with Parkinson's, which limits his balance and mobility. He recently spent six days in an inpatient rehabilitation program after being hospitalized in Washington on July 16. And his statement Wednesday disclosed for the first time his kidney surgery.

A successful real estate agent before he entered politics, Isakson ran for office in his 20s and quickly emerged as a rising star. Back then, Republicans were a rarity in state politics: By the time he took over as the Georgia House’s top Republican in 1983, there were only 24 GOP lawmakers in the 180-member Georgia House.

He helped build the Georgia GOP from his Cobb County base, but he also is known for a bipartisan streak that includes cutting deals with Democrats and occasionally offering up candid criticism of President Donald Trump and other Republicans.

His retirement triggered praise from state leaders from both parties. Kemp said “no one embodies the heart and soul of Georgia more than Johnny Isakson," and the governor added that the state is “immeasurably blessed” by his leadership.

"What Georgia should be most thankful for is the high standard that Johnny held as a true gentleman, a fighter for his constituents, a trusted advocate for our nation’s veterans, and one of the greatest statesmen to ever answer the call of service to our country,” Kemp said.

State Sen. Nikema Williams, the chairwoman of the Democratic Party of Georgia, thanked Isakson for his “years of service to his state and country,” and she predicted that his retirement will clinch Georgia’s status as a swing state.

“We are the battleground state, and Georgia Democrats are ready to fight and deliver both the Senate and the presidency for Democrats across the country in 2020,” she said.

Isakson said he will return to Washington on Sept. 9 when the Senate goes back into session, and he offered a hint about his post-retirement plans.

“And after December 31, I look forward to continuing to help the people of Georgia in any way I can and also helping those who are working toward a cure for Parkinson’s.”

Here’s Isakson’s full statement:

“After much prayer and consultation with my family and my doctors, I have made the very tough decision to leave the U.S. Senate at the end of this year. I have informed Georgia Governor Brian Kemp today that I will resign my Senate seat effective December 31, 2019.

“I am leaving a job I love because my health challenges are taking their toll on me, my family and my staff. My Parkinson’s has been progressing, and I am continuing physical therapy to recover from a fall in July. In addition, this week I had surgery to remove a growth on my kidney.

“In my 40 years in elected office, I have always put my constituents and my state of Georgia first. With the mounting health challenges I am facing, I have concluded that I will not be able to do the job over the long term in the manner the citizens of Georgia deserve. It goes against every fiber of my being to leave in the middle of my Senate term, but I know it’s the right thing to do on behalf of my state.

“I look forward to returning to Washington on September 9 when the Senate goes back into session. And after December 31, I look forward to continuing to help the people of Georgia in any way I can and also helping those who are working toward a cure for Parkinson’s.”