"I think we have to assume that a referendum having been passed with a lot of attention, a lengthy campaign and relatively high participation rates is going to stick," Obama said when asked if Britain could go back on the vote.
The Brexit vote shocked Britain's allies, with Obama having strongly backed the remain camp ahead of last month's referendum, citing the possible impact on Britain's key role in world affairs as a major concern.
"Our primary interest is to make sure that the negotiations and this process are as orderly and as sensible as possible."
On Friday, Obama insisted that Brexit would not undermine Britain's role in NATO but urged London and Brussels to avoid "protracted, adversarial negotiations" over their divorce.
"How the negotiations work, I think is going to be up to the parties involved," the president said Saturday.