John Podesta, a top adviser to the former first lady and secretary of state, made her 2016 plans official with an email message sent to veterans of her first presidential campaign.
“I wanted to make sure you heard it first from me – it’s official: Hillary’s running for president,” the email said. It went on to say that Mrs Clinton will soon meet voters in Iowa and will host a formal “kick-off” event some time next month.
Later last night, Mrs Clinton launched her campaign website, telling Americans she wanted to be their “champion”.
Mrs Clinton ran for the Democratic presidential nomination in 2008 but lost to Barack Obama.
The overwhelming Democratic favourite, she had been expected to declare her candidacy for months.
In a video on her website, Mrs Clinton declared: “I am running for president”.
“Americans have fought their way back from tough economic times,” she said, “but the deck is still stacked in favour of those at the top.
“Everyday Americans need a champion and I want to be that champion,” she added.
She is now expected to travel to Iowa and New Hampshire, two early primary contests in the 2016 race.
After her failed nomination bid in 2008, Mrs Clinton served as secretary of state in Mr Obama’s first administration (2009-2013).
Known for her punishing travel schedule – she visited 112 countries in four years – she led the US response to the Arab Spring and the military intervention in Libya in 2011.
Mr Obama praised Mrs Clinton, saying at a news conference at the Americas summit in Panama on Saturday that she would make an “excellent president”.
And her successor in the post, John Kerry, called her a “good friend”, telling ABC’s This Week programme she “did a terrific job of rebuilding alliances that had been shredded over the course of the prior years”.
But Republican presidential contender Rand Paul criticised Mrs Clinton for her handling of a September 2012 attack on a US diplomatic compound in Benghazi, Libya, in which the US ambassador was among those killed.
He also said questions remained about funds received by a charity set up by Mr and Mrs Clinton. “There is a history of the Clintons feeling they are above the law,” the Kentucky senator said on CNN’s State of the Union programme.
Two prominent Republicans have officially entered the race for their party’s nomination – Mr Paul and Texas senator Ted Cruz. Former Florida governor Jeb Bush is another frontrunner.
As a senator, Mrs Clinton voted for the invasion of Iraq in 2003 but distanced herself from the way the war was waged, and called for US troops to be withdrawn.
During her husband’s first term as president, she campaigned for healthcare reform but her plan fell apart and never made it to a vote in Congress.
Mrs Clinton stood by her husband when he was exposed as having had an affair with a White House intern, Monica Lewinsky.