"I'm running for president. Everyday Americans need a champion, and I want to be that champion," the 67-year-old former secretary of state said, emerging as one of the top contenders for the Democratic party.
The announcement came first in a tweet with an accompanying video and then in an email to her supporters.
The one-time first lady enters the race seven years after her bitter nomination defeat to President Barack Obama in 2008.
In an accompanying video, Clinton pledged to be a champion for everyday Americans and their families.
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She said she believes this campaign is about voters, not her, and urged people to get involved in her campaign saying, "It's your time."
The video features middle class families talking about their lives and planning for what is ahead.
In the video, Clinton explained why she is running, saying, "Americans have fought their way back from tough economic times but the deck is still stacked in favour of those at the top."
The wife of former president Bill Clinton said she is committed to earning every vote and is starting with a focus on the early Democratic primary states. She will start with stops in Iowa this week to talk with Iowa voters, ramping up to a campaign kickoff in mid-May.
Clinton, a globe-trotting diplomat, surprised her party by serving dutifully under Obama who had defeated her.
A day earlier, Obama had said that Clinton would be a great president.
As secretary of state in the Obama administration from 2009-13, she stood by India on many occasions, especially on the subject of terrorism.
During her visit to Islamabad in 2011, Clinton had said Pakistan should not keep "snakes" in the backyard to bite its neighbours.
During her time in office, the US and India worked to ensure closer cooperation in high technology areas, particularly defence and space. The two sides also launched a ministerial-level strategic dialogue in July 2009.