Powell, who also served in the Reagan and George H.W. Bush administrations, backed President Barack Obama in both the 2008 and 2012 campaigns. He announced his plan to a Long Island group during a luncheon.
The announcement was confirmed by Powell's chief of staff, Peggy Cifrino.
Aides informed Clinton of Powell's support after her early voting rally Tuesday afternoon in Florida. She is grateful for his support, one aide said.
Later, Clinton's campaign tweeted, "Proud to have the endorsement of General Powell, a decorated soldier and distinguished statesman," signed with an "H" indicating her personal approval.
The former chairman of the Joint Chiefs of Staff has had tough words for both major party candidates.
Hacked emails released in September showed Powell strongly condemning Trump, labeling him a "national disgrace and an international pariah."
In one email dated August 3, Powell wrote, "Trump is nuts. Everybody wants me to speak out, but I will pick the time and place for maximum effect like I did in 2008 and 2012. Right now, Trump is his worst own enemy."
At the time, an aide to Powell said the emails were "accurate" but declined further comment.
Powell and Clinton, meanwhile, have had an at-times difficult relationship. He repeatedly pushed back against reports over the summer suggesting that he might have given Clinton the idea to use a private email account as secretary of state, telling media outlets in August that "her people are trying to pin it on me."
Despite Powell's support for the Democratic presidential nominee in the last three cycles, he insisted in September 2015 that he was still a Republican.
"I'm still a Republican because I believe in a strong defense, because I believe in the entrepreneurial spirit that is so typical of the Republican Party in the past," Powell said at the time.
"But," he continued, "I'm having difficulty with the party now."
Clinton has earned the support of other high-profile Republicans, including former Sen. Larry Pressler
, Sally Bradshaw
(who was a senior adviser on Jeb Bush's campaign) and Hewlett Packard CEO Meg Whitman
and ex-Reagan political director Frank Lavin
And according to sources, George H.W. Bush said he will vote for Clinton