"Every president is tested by world events, but Donald Trump thinks about how his golf resort can profit from them," intones the 30-second ad released Sunday while showing coverage of Friday's vote and the reaction in world markets. "In a volatile world, the last thing we need is a volatile president."
The ad entitled "Tested" fits into a narrative the Clinton campaign is pushing on how Trump is a craven businessman in politics only for himself.
Click through some of Donald Trump's most controversial tweets:
Clinton herself has yet to respond to the "Brexit" vote on-camera or by phone, although aides say the presumptive Democratic nominee would probably address the issue later on Sunday when she returned to the campaign trail.
Despite a shakeup in world markets caused by the U.K. referendum and a plummeting of the value of the British pound, Trump in a trip to his golf course in Scotland Saturday said the Brexit wouldn't mean much for Americans.
"Well, Americans are very much different, this shouldn't even affect them," Trump said.
"The United States has real, real problems and a Brexit is not their problem," he said at another point.
The ad also shows a clip of Trump in Scotland saying the fall of the British currency could mean more people visit his golf resort there.
"When the pound is down, people come to Turnberry," Trump said Friday, referring to his Scottish golf resort.
Voters in the U.K. voted on Friday to leave the EU. Some have wondered whether the populism and resistance to authority that was seen as driving the Brexit vote could boost Trump's chances in the U.S. presidential election.
The new ad will air nationally on cable starting this week. Clinton's campaign also released a video Friday mocking Trump's comments about his golf course in Scotland following the Brexit vote.