"We will work with the governments of Sudan and Southern Sudan to ensure a smooth and peaceful transition to independence," Obama said in a statement.
"After decades of conflict, the images of millions of southern Sudanese voters deciding their own future was an inspiration to the world and another step forward in Africa's long journey toward justice and democracy," he said.
"Now, all parties have a responsibility to ensure that this historic moment of promise becomes a moment of lasting progress. The Comprehensive Peace Agreement must be fully implemented and outstanding disputes must be resolved peacefully," Obama said.
At the same time, there must be an end to attacks on civilians in Darfur and a definitive end to that conflict, he noted.
Southern Sudan is slated to become the world's newest country in July. Final results from last month's independence referendum announced on Monday show that 98.8 per cent of the ballots cast were for secession from Sudan's north.
In her remarks, Secretary of State Hillary Clinton said that the US is looking forward to working with southern leaders as they undertake the tremendous amount of work to prepare for independence in July and ensure the creation of two viable states living alongside each other in peace.
"The Government of Southern Sudan must launch a process of inclusive governance and take steps to improve good governance and service delivery, as well as to adopt long-term security and economic arrangements with the North," she said.
Clinton also announced that the US is now initiating the process of withdrawing Sudan's State Sponsor of Terrorism designation, the first step of which is initiating a review of that designation.
"Removal of the State Sponsor of Terrorism designation will take place if and when Sudan meets all criteria spelled out in US law, including not supporting international terrorism for the preceding six months and providing assurance it will not support such acts in the future, and fully implements the 2005 Comprehensive Peace Agreement, including reaching a political solution on Abyei and key post-referendum arrangements," she said.
"It marks a new day in the region," White House Press Secretary Robert Gibbs said. The US commends the Government of Sudan for accepting its outcome and looks forward to working with the Republic of Southern Sudan when it joins the community of nations in July 2011, said US Ambassador to the UN Susan Rice.