Trump on Tuesday called the deal "ridiculous", but did not say whether he would withdraw the USA by the May 12 deadline he has set.
Without mentioning Trump by name, he challenged the Republican president's protectionist and nationalist impulses and said modern economic and security challenges must be a shared global responsibility that is "based on a new breed of multilateralism".
Macron went on to contradict Trump's positions on a number of issues. According to TIME Magazine, "Trump had all but endorsed Macron's right-wing opponent, Marine Le Pen, past year before the election, and Le Pen ran on numerous views Macron was arguing against in his speech".
But Macron's speech underscored the very real differences he harbors with his USA counterpart.
Iran has also said it would ramp up enrichment of radioactive fuel if Trump walks away from the accord.
French President Emmanuel Macron received a warm, three-minute standing ovation from US lawmakers Wednesday before delivering - in English - a rare address to Congress that underlined the allies' differing policy goals. The original five nuclear weapons powers - the United States, Russia, Chian, Britain and France - would also phase out their arsenals.
But following that history lesson, all bets were off.
The deal is up for review on May 12, with Trump having repeatedly threatened to scrap it if Tehran does not make concessions regarding its ballistic missile program - which was never part of the original agreement.
Macron told Congress: "The United States is the one who invented this multilateralism".
He demanded again that the United States do its part to provide future generations with "a planet that is still habitable in 25 years". "We are killing our planet - let us face it, there is no Planet B".
Problems should be solved, he said, by negotiating at the World Trade Organization, an institution that Mr. Trump recently called "a disaster" that enforces global trade rules. "We wrote these rules".
"We must find a smoother transition to a lower carbon economy", he said.
Macron said he believed he had persuaded Trump that his hopes for ending United States involvement in Syria would create new problems.
But during his visit to the US, Macron said he spoke to the US president about a "new deal" through which the US and Europe would tackle Trump's concerns about Iran's nuclear program and beyond. "That is why we can not say we should rid of it like that".
"I have spoken with Macron several times by phone, and one time in person at length".