US President Barack Obama put his political weight behind his ally David Cameron, calling unequivocally for Britain to remain in the European Union, but despite his popularity Obama's calls seemed to fall on deaf ears.
Just months after his remarks alongside Cameron in London, Obama could only fall back on assurances that the "special relationship" between the US and Britain would remain in spite of the decision by British voters to leave the EU.
The relationship, however, could soon have more in common than Obama had in mind if the Brexit proves to be the writing on the wall for US presidential elections.
Republican Donald Trump, who hopes to replace Obama in the Oval Office, was likely watching the British vote especially closely. Trump landed in Scotland as results of the vote became known and praised Britons for taking back their country.
He pointed to parallels between the vote and the US election, calling on Americans to "re-declare their independence" in November by rejecting the global elite like their British counterparts.
If observers move beyond the superficiality of political champion of Britain's "leave" campaign Boris Johnson and Trump's hair, and look at the voters they may see similarities between the situations in both countries.
Bboth nations have been shaken by globalization with older, white voters expressing alienation from the political system. Wages are stagnating and immigration policy is promoting division. Economic populism and appeals to racial resentment are on the rise, while facts are ignored and the political elite seem divided from the rest of society.
In Britain, the risky unknown triumphed over the status quo, The New York Times noted. Expertise was swept aside for change, the Washington Post observed, noting it would be difficult for Democrats in November 8 elections if change remains a primary concern of voters.
In the US, Trump had been the favoured candidate of Republicans who rejected the party establishment, while Democrat Hillary Clinton must now win over millions of Bernie Sanders supporters whose anti-establishment economic populism had appealed to voters who are now being actively courted by Trump.
The Brexit itself will likely play little role in US elections that tend to be dominated by domestic affairs. But the resulting global economic uncertainty could play a factor, and Clinton sought to play on those concerns Saturday.
The referendum's result prompted a sell-off on global markets that hit US families in their retirement accounts, but Trump "cheered and celebrated," Clinton advisor Jake Sullivan said.
Trump, who was visiting his golf resorts on Scotland, praised Britons for asserting their independence and noted a weaker pound would draw more tourists to his resort.
"At a time when the world looks to the United States for steady leadership, Donald Trump once again proved two truths about his candidacy - that he is temperamentally unfit to be president of the United States and that he is in it for no one but himself," Sullivan said.
The Transatlantic Trade and Investment Partnership trade deal currently being negotiated between the US and the EU could also be at risk on several fronts amid the votes. The exit of Britain from the EU changes the frame of negotiations, while rising anti-free trade sentiment on both sides of the Atlantic is also a growing threat.