At the same time, as the most powerful country in the world, the United States values the status quo and the leadership Great Britain has exercised within the European Union and beyond.
The vote is the beginning of a lengthy transition as Britain reconstructs its regional and global role.
Notwithstanding admonitions by the Leave campaign that the vote was none of the Yanks' business, America has a significant stake in what happens now, given the important alliance between the two countries.
So how will Brexit affect the special relationship?
The US and UK are bound by history, culture, trade, democratic values and shared interests. There is every reason to believe Washington and London will work through all bilateral issues that arise, including new trade arrangements.
New deal?
Wading into the controversy in April, President Barack Obama warned that in the event of a Leave victory, Great Britain would be at the "back of the queue" regarding a new trade agreement. The Obama administration will be devoting its energy to ratification of the Trans-Pacific Partnership.
Since Prime Minister David Cameron signalled it will be some time before Article 50 is triggered,  a new deal will fall to new governments on both sides.
Given the depth of US-UK bilateral investment, a new deal will get done, although the politics on both sides will be tricky. To some extent, the US presidential and Leave campaigns are mirror images.
Substantial numbers of voters in both countries believe they have been short-changed. It will take heavy political lifting in Washington and London to convince their sceptical electorates that the end result is a better deal for both.
Less clear is what happens to Great Britain and the European Union as they go through this process. For London and Brussels, how do the new UK government and reduced EU alliance interpret the mandate or message from the Brexit vote?
And is there a capacity and political will for determined action when the dust settles?
Here in the United States, there is an enduring myth that politics should stop at the water's edge. It never has and never will. In this case, the Brexit vote has fundamentally altered British foreign policy and the western international structure, which indirectly affects American foreign policy as well.
This is a political earthquake and there could be further aftershocks.
England and Wales voted to Leave and Scotland and Northern Ireland voted to Remain. The fissures in British society exposed by the Scottish independence referendum will only deepen in light of the Brexit vote.
The US will always value Great Britain, but its composition is once again up for discussion.
Great Britain is likely to enter a period of political retrenchment as it negotiates its unprecedented divorce from the EU while it works to preserve its marriage with two units that see value in a European identity.
When Europe embarked on its remarkable integration project, Henry Kissinger famously questioned whom Washington should call.
While Brussels has become a key hub for American diplomacy, particularly with the renewed relevance of Nato (and greater emphasis on its traditional mission in light of the crisis in Ukraine) and evolution of the European Defence Agency, Washington always had London, Paris and Berlin on speed dial.
Brexit doesn't change the importance of American collaboration with key European allies, but gaining a consensus for determined action - always a challenge with the EU at 28  - will become more complex with Europe at 28 minus one.
The Brexit vote will surely exacerbate the existing anti-establishment and anti-immigration sentiment in various corners of the continent.
The risk is that a Europe preoccupied with redefining its internal and external relationships will be less able to deal coherently with the ongoing migration crisis, its support for Ukraine and sanctions against Russia.
Key European allies, to borrow a favourite Obama phrase, will be inclined to devote more resources to "nation-building at home." Nato has encouraged its members to devote 2% of their gross domestic product to defence. Most have fallen short.
Brexit will make that an even greater challenge, particularly for Great Britain, which will experience significant near and mid-term costs as it rewires its economy.
There are good reasons to believe that both the United Kingdom and European Union will make the new arrangement work.
The unanswerable question in Washington is what challenges lurk as they shift from the region that is to the one that will be. At the end of that journey, we know that key relationships will endure. What we don't know is whether they will be more effective.
P.J. Crowley is a former U.S. Assistant Secretary of State, a distinguished fellow at The George Washington University Institute for Public Diplomacy & Global Communication and author of the forthcoming book, Red Line: American Foreign Policy in a Time of Fractured Politics and Failing States.
There is a revolutionary strain in the American DNA - Great Britain knows all about that - so on the other side of the Atlantic there is an understanding of the statement the British people made with the Brexit vote.