Chafee, a onetime Republican U.S. senator and later an Independent-elected governor, announced his plans at George Mason University, making him the fourth Democrat to seek the party's nomination.
He simultaneously announced his candidacy on Twitter.
"Today I am formally entering the race for the Democratic nomination for President #Chafee2016," he wrote.
On the Republican side, the list of candidates is much longer: S.C. Sen. Lindsey Graham, former New York Gov. George Pataki, former Pennsylvania Sen. Rick Santorum, neurosurgeon Ben Carson, Texas Sen. Ted Cruz, former HP CEO Carly Fiorina, former Arkansas Gov. Mike Huckabee, Kentucky Sen. Rand Paul and Florida Sen. Marco Rubio.
Chafee, 62, said he plans to focus his campaign on helping the middle class by increasing the minimum wage and supporting social programs that include Head Start. He plans to target front-runner Clinton on her vote to authorize the Iraq War when they both served in the Senate, an issue that became problematic for Clinton in her 2008 bid. Chafee was the only Republican senator to oppose the use of military force in Iraq in 2002.
"I don't think anybody should be president of the United States that made that mistake," Chafee told The Washington Post in April. "It's a huge mistake, and we live with broad, broad ramifications today—of instability not only in the Middle East but far beyond and the loss of American credibility. There were no weapons of mass destruction."
Chafee's GOP roots date back to his great-great uncle, great-great grandfather and father, all serving as Republican governors of Rhode Island. Chafee himself was a Republican, albeit far less conservative than his colleagues, until 2007, when he split with the GOP to be an Independent endorsed Barack Obama for president in the 2008 Democratic primary. By 2013, he had joined the Democratic Party.