The former US first lady, senator and secretary of state has said she will run for president in 2016, making the announcement in a video posted on her website.
"Americans have fought their way back from tough economic times, but the deck is still stacked in favor of those at the top," she said in the video.
"Everyday Americans need a champion and I want to be that champion. So you can do more than just get by - you can get ahead and stay ahead," she added.
Clinton enters the race as the overwhelming favorite to win the Democratic Party's nomination to run for president in the November 2016 election.
Even before she made her latest presidential bid official, potential Republican Party candidates were already taking aim at the 67-year-old Clinton, in particular over her record as secretary of state during President Barack Obama's first term in office.
"We must to do better than the Obama-Clinton foreign policy that has damaged relationships with our allies and emboldened our enemies," former Florida Governor Jeb Bush said in a video released by the political action committee Right to Rise.
Bush, the brother of former President George W. Bush, has not yet announced whether he will run for the Republican nomination.
Kentucky Senator Rand Paul, who formally announced his candidacy for the Republican nomination last week, also made the rounds of US Sunday political chat shows, criticizing the former secretary of state for, among other things, her handling of a 2012 attack on a US diplomatic compound in the Libyan city of Benghazi.
The Republicans have also criticized her for using her private email account while secretary of state.
Support from Obama
On Saturday, though, Clinton, who was the American first lady when her husband Bill was president from 1993 to 2001, received a vote of confidence from her former boss and the man who defeated her for the 2008 Democratic Party nomination.
"She was a formidable candidate in 2008.... She was an outstanding secretary of state," Obama said at a regional summit in Panama. "I think she would be an excellent president."
Obama is constitutionally barred from seeking a third term as president.
Currently, Clinton is ahead of most of her potential Republican candidates in US opinion polls.
pfd/rc (AFP, Reuters)