She praised the agreement which will see policing and justice powers devolved from Westminster to the Stormont Assembly by April 12.
The deal was announced with First Minister Peter Robinson and Deputy First Minister Martin McGuinness at Hillsborough Castle, Co Down, where the Democratic Unionist Party (DUP) and Sinn Fein held nearly two weeks of round-the-clock negotiations.
Mrs Clinton said: "Today, Northern Ireland has taken another important step toward a full and lasting peace.
"Its political leaders have agreed on a roadmap and a timeline for the devolution of policing and justice powers, and they have taken other productive steps as well. The accord they reached today will help consolidate the hard-won gains of the past decade."
She added: "This has not been an easy road. There were plenty of bumps along the way. I have been in regular contact with the parties since my trip to Belfast in October, and I know that at times the path forward was far from clear."
Mrs Clinton praised those who brokered the deal and promised her continued support for the peace process and the efforts to foster economic links across the Atlantic.
"Now, we join the world in looking to the leaders of Northern Ireland to build upon their efforts by promoting a new spirit of cooperation among all parties," she said.
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