The decision comes after Perdue last week filed Federal Election Commission paperwork to become a candidate in the 2022 midterms. Perdue lost reelection to Sen. Jon Ossoff, D-Ga., during Georgia's Senate runoff election on Jan. 5.
"After much prayer and reflection, Bonnie and I have decided that we will not enter the race for the United States Senate in Georgia in 2022," Perdue said in a statement Tuesday. "This is a personal decision, not a political one."
"I am confident that whoever wins the Republican Primary next year will defeat the Democrat candidate in the General election for this seat, and I will do everything I can to make that happen," Perdue continued. "As we saw in my race in November, Georgia is not a blue state. The more Georgians that vote, the better Republicans do."
He added: "These two current liberal US Senators do not represent the values of a majority of Georgians."
Perdue said he is "hopeful" that Georgia officials will "correct the inequities in our state laws and election rules so that, in the future, every legal voter will be treated equally and illegal votes will not be included."
"I will do everything I can to be helpful in this effort," he said, adding that "it has been the honor of my life to have represented the people of Georgia in the United States Senate."
"Bonnie and I want to thank my fantastic staff and everybody in the state and around the country for all the help they have given us," he continued. "May God continue to bless Georgia and the United States of America."
Perdue’s decision comes after he filed FEC paperwork, and after a source familiar told Fox News that Perdue would not be running for his old seat, as it would not be up for re-election, but rather the seat now held by Freshman Sen. Raphael Warnock, D-Ga.
Warnock defeated Sen. Kelly Loeffler, R-Ga., who was appointed by Georgia Gov. Brian Kemp.
The speculation surrounding Perdue’s potential run came as Herschel Walker's name had been increasingly mentioned in Republican circles as a potential 2022 Senate candidate in Georgia. Walker has been a major supporter of former President Trump.
Also, earlier this month, former Rep. Doug Collins, another major Trump supporter in Georgia, and who ran in the 2020 special election against Loeffler, also was seriously mulling a 2022 Senate bid in the state.
"I think this would freeze the field," a veteran GOP strategist in Georgia said of the filing by Perdue. "The field is now officially frozen until David says he's in or he's out."
The strategist told Fox News that if Perdue ends up launching a 2022 campaign, Collins would not run.
Fox News' Mike Emanuel and Paul Steinhauser contributed to this report.