US forces struck the B1 highway bridge linking Tehran with Karaj on Thursday, targeting what military officials described as a planned supply route for Iran's missile and drone forces.
The operation killed at least eight people and injured dozens, including civilians outdoors during the Nowruz holiday.
President Donald Trump hailed the strike in a social media post, declaring, "The biggest bridge in Iran comes tumbling down, never to be used again - Much more to follow! IT IS TIME FOR IRAN TO MAKE A DEAL BEFORE IT IS TOO LATE, AND THERE IS NOTHING LEFT OF WHAT STILL COULD BECOME A GREAT COUNTRY!"
US officials said the strike forms part of a broader effort to disrupt Iran's military logistics and prevent the movement of missile and drone components across the country.
Iranian leaders responded defiantly. Parliament Speaker Mohammad Ghalibaf stated, "When it comes to defending our homeland, each and every one of us will become a soldier of this country," adding that Iranians remain 'armed, ready and standing'.
Tehran ruled out negotiations, with a foreign ministry spokesman calling talks 'impossible under current conditions'.
The bridge strike coincided with other attacks on infrastructure.
Iranian authorities reported an airstrike on the Pasteur Institute of Iran, a major public health facility, which a health ministry spokesman condemned as a 'direct assault on international health security'.
The conflict has, however, reverberated across the region. Israel intercepted missiles from Iran, and Houthis in Yemen launched a missile toward Israel.
Diplomatic efforts remain stalled, with Russia, China and France blocking a UN Security Council bid to authorise force to reopen the Strait of Hormuz.