AP Photo/Pablo Martinez Monsivais
"The people of the United Kingdom have spoken, and we respect their decision," Obama said.
He continued: "The special relationship between the United States and the United Kingdom is enduring, and the United Kingdom's membership in NATO remains a vital cornerstone of US foreign, security, and economic policy."
The president sought to reassure the EU that the US would continue to have a strong relationship with it.
"So too is our relationship with the European Union, which has done so much to promote stability, stimulate economic growth, and foster the spread of democratic values and ideals across the continent and beyond," he said.
Obama added: "The United Kingdom and the European Union will remain indispensable partners of the United States even as they begin negotiating their ongoing relationship to ensure continued stability, security, and prosperity for Europe, Great Britain and Northern Ireland, and the world."
Obama was an opponent of the so-called Brexit, saying in April he wanted the UK to remain a part of the EU. At the time, he warned that the UK could fall "to the back of queue" when negotiating trade deals with the US if it decided to abandon the political-economic union.
The UK shocked the world on Thursday when it voted to abandon the EU. Markets plunged into chaos, and British Prime Minister David Cameron announced he would resign.