"I am leaving a job I love because my health challenges are taking their toll on me, my family and my staff," Isakson said in a statement. "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."
Isakson, 74, won a six-year term in 2016. His term is due to end in 2022.
“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," he said.
“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.”
Isakson holds the distinction of being the only Georgian ever to have been elected to the state House, state Senate, U.S. House and U.S. Senate. In addition, in 2016 he became the first Georgia Republican ever to be elected to a third term in the U.S. Senate.
Isakson is chairman of both the Senate Ethics Committee and the Senate Veterans Affairs Committee, and he remains the only Republican in the Senate chairing two committees.
According to Georgia state law, Republican Gov. Brian Kemp will appoint a replacement to the seat that will serve until the next statewide election, which in this case will take place in November 2020.
This means both of Georgia's Senate seats will be up in 2020.
ABC News' John Verhovek contributed to this report.