The US military's Central Command said it completed a wave of strikes against Islamic Revolutionary Guard Corps targets on Tuesday, including air defence sites, radar systems, maritime assets and facilities, mine-laying capabilities, and communications sites.
Iranian media reported attacks on multiple targets around the country on Tuesday, many near the Strait of Hormuz, where Iran has been threatening oil tankers that dare transit the narrow waterway without authorisation.
Iran in turn said it struck US assets in Jordan and Iraq, according to official statements, while Iranian media reports said it also attacked Bahrain.
Although the IRGC said it killed a large number of US forces in Jordan, two US officials told Reuters there had not been any casualties, according to initial assessments.
Jordan's armed forces said its air defence systems dealt with 13 ballistic missiles that entered the kingdom's airspace, 10 of which were intercepted and three fell in remote areas. Bahrain said Iranian drones were intercepted and destroyed.
The IRGC also said its ground forces carried out combined missile and drone attacks on US bases in Erbil in northern Iraq, killing several US personnel. Neither Iraq nor the US confirmed the attack.
The exchange of fire marked the first serious combat since July, ending a period in which the warring parties withheld fire but also showed little interest in returning to negotiations.
The lull came as the conflict appeared to be draining both sides.
Iran's already ailing economy has been battered by war and its conventional military forces have been degraded.
Meanwhile, with US President Donald Trump confronting higher fuel prices ahead of November congressional elections, the US Army has used up much of its global stockpile of highly accurate long-range missiles, raising concerns about the military's readiness for future conflicts.
Nonetheless, the renewal of hostilities produced another exchange of defiant statements.
"I like our position now much better, with almost total control of the Hormuz Strait, and their economy totally collapsing," Trump said.
"They are just playing out the inevitable. When are the Iranian people going to rise up and fight?"
Iran's joint military command responded in kind.
"We warn that the continuation of American evil in the region will be met with heavier, more widespread, and devastating responses, and any country that cooperates with the aggressive American army must accept its dangerous consequences," it said in a statement.
In what could be one of the more significant cases of civilian casualties in the war, five people were killed and 50 wounded at a wedding near Sirik, a coastal area on the Strait of Hormuz, the Iranian Red Crescent reported.
The Mehr news agency said a four-year-old child was among those killed, while the IRNA news agency, citing a provincial official, put the number of wounded at 68.
"Make no mistake: these crimes will not go unpunished," Ebrahim Azizi, chairman of the Iranian parliament's National Security and Foreign Policy Committee, said on X.
Iran's foreign ministry issued a statement pledging that Iran would respond to "these savage crimes with firmness".
"Those governments and international institutions that remain silent in the face of such barbarism, or seek to justify such acts, must understand that their silence is not neutrality," Iran said.
"Those who remain silent today will not be immune to its consequences tomorrow."