Trump risked sparking a diplomatic crisis with France, Germany and the U.K. — three parties to the deal — and the broader European Union if he refused to issue the waivers. Restoring sanctions against Iran, OPEC's third-largest oil producer, also threatened to roil energy markets and put a freeze on billions of foreign investment into the country.
The structure of the deal has created a recurring thorn in Trump's side. The sitting president must suspend various sanctions every 120 to 180 days. Three key waivers were scheduled to expire in the coming days, with the next deadline to certify the deal to Congress also landing this week.
Even with the waivers in the rearview mirror, analysts say the agreement remains on shaky ground. Risk consultancy the Eurasia Group gives the deal a 55 percent chance of surviving Trump's first term, while RBC Capital Markets says the prospects for the accord are "bleak" in 2018, given the constant threat of sanctions snapping back into place.
Cliff Kupchan, chairman of the Eurasia Group, maintained his odds for the deal's survival. Some of the changes Trump is seeking would not take effect for six years, so it's possible the Iranians will wait to see if Trump gets re-elected.
"The Europeans won't agree to snap back their sanctions based on US triggers, but they may be able to satisfy Trump with rhetorical support," he told CNBC in an email.
"It all depends on the wording of the emerging bill — if it tears up the deal now, it's over. If it's 6 years hence, it lives," he said.
Mark Dubowitz, CEO of the Foundation for Defense of Democracies, said the Europeans have every incentive to cooperate on modifying the deal.
"If they don't, by May of this year, President Trump will cancel America's participation in the deal and unleash powerful secondary sanctions that will deter most European companies and banks from doing business in Iran," he said in an email.
"Many are already sitting on the sidelines because of these fears. Many more will stay there if American sanctions are reinstated."
As a candidate, Trump threatened to scrap the deal, but several of his top advisors have implored him to preserve it. They have counseled him to instead apply pressure with new sanctions targeting Iran's ballistic missile program and elements of its security apparatus accused of aiding U.S.-designated terror groups and sowing instability throughout the Middle East.
The Trump administration is seeking support from European countries to address Iranian ballistic missile tests, isolate the Revolutionary Guard and modify the Iran nuclear deal.
Trump and Republicans want to prevent the expiration of key provisions of the deal scheduled to phase out in 10 to 15 years, including limits on Iran's access to nuclear material and advanced equipment. It also wants to expand international inspectors' access to Iranian military sites.
On Thursday, ahead of Trump's decision, European nations jointly implored the United States to keep the deal in tact.
"The accord is essential and there is no alternative," France's foreign minister, Jean-Yves Le Drian, told reporters. "We do not hide the other points of disagreement (with Iran) that exist."
Trump's refusal in October to certify to Congress that Iran is complying with the deal gave lawmakers the option to restore sanctions against Iran. Instead, senators agreed to work with the Trump administration to change the terms of the accord through new legislation.
U.S. Sen. Bob Corker, the Republican chairman of the Senate Foreign Relations Committee, acknowledged last week that Congress would not be ready to present Trump with legislation before this week's waiver deadlines. There is little evidence that the Senate's legislative effort has advanced much beyond a framework Corker released in October.
That plan sought to make the nuclear deal essentially permanent, a proposal that upends the accord the Obama administration negotiated. Iran has dismissed that option, saying it violates the agreement, and the proposal remains a tough sell for Democrats and European allies.
Corker's plan reflects a new strategy outlined by Secretary of State Rex Tillerson in October. It would create red lines that, if crossed by Iran, would automatically restore sanctions.
Sen. Ben Cardin, the Democratic ranking member of the Senate Foreign Relations Committee, says he remains open to discussing legislation, but said Trump's actions on Friday had set back the bipartisan process, which he has been engaging in with Corker.
"Instead of leading an international negotiation on the agreement himself, however, the President's statement making threats and dictating final terms of potential negotiations with Congress and Europe makes it more challenging to achieve this objective," he said in a statement.
On Thursday, the Justice Department announced it was forming a team of prosecutors to counter an alleged organized crime ring operated by Hezbollah, a Shiite political and militant group in Lebanon backed by Iran.
The Treasury Department has also applied new sanctions against Iran's Revolutionary Guard, a hard-line security force with financial interests through the domestic economy.
— CNBC's Kayla Tausche, Kevin Breuninger and Reuters contributed to this story.