The clashes mark one of the biggest exchanges in hostilities since the two countries agreed to a ceasefire in April and came after US President Donald Trump said Iran had downed a US Apache helicopter near the strait on Tuesday.
"I believe the response should be very strong, very powerful, and that's what this one is," Trump told ABC News on Tuesday.
The escalation in violence deepens doubts about the prospects for a deal to end the war that started on February 28 with joint US-Israeli strikes against Iran.
Tehran responded by firing on Gulf neighbours that host US bases and all but choked off the strait, a vital conduit for oil and gas.
The latest US strikes on Wednesday targeted Iranian air defence, ground control stations and surveillance radar sites, according to the US military.
A US official said almost 20 Iranian targets had been struck.
The Islamic Revolutionary Guard Corps (IRGC) said Qeshm island and the port city of Sirik in the Strait of Hormuz came under attack, while explosions were heard in Bandar Abbas and later near Jask at the entrance to the strait, Iranian media reported.
The IRGC said it had attacked US military bases in Bahrain, Kuwait and Jordan with drones, and missiles in response to the new "US aggression".
Four sites were targeted at the US al-Azraq base in Jordan using long-range missiles, and the IRGC warned it was ready to deliver a "crushing and decisive" response to any further US attack.
Jordan's military said on Wednesday it had intercepted and shot down five missiles launched from Iran towards al-Azraq.
The Kuwaiti army said its air defence systems were engaging hostile aerial targets, while Bahrain's air defences had repelled Iranian attacks.
Iran's foreign ministry condemned US strikes in the country's south, saying Tehran acted in self-defence, and warned Gulf states they would face consequences if their territory was used by US or Israeli forces.
A US official, speaking on condition of anonymity, said initial assessments showed nearly all Iran's missiles and drones were intercepted, with no harm to personnel or US locations.
On Tuesday, a US Apache helicopter was brought down by a one-way Iranian attack drone, according to a US official who spoke on condition of anonymity.
Two US pilots involved in the helicopter incident were uninjured, Trump said.
Iran's state media reported that no offensive air operations had been conducted in the Strait of Hormuz in the previous 24 hours.
A US Navy surface drone found and rescued the two crew, the US military said, after the army attack helicopter went down in waters near Oman's coast while on patrol early on Tuesday.
The US military's Central Command gave no reason for the crash.
It said the two crew were rescued after two hours and said they were in stable condition - a more cautious assessment than Trump's description.
Iranian Foreign Minister Abbas Araqchi did not directly address the helicopter incident, but posted on X that foreign forces in the region risked being involved in accidents or crossfire.
"To reduce risk, best solution is for them to leave," he wrote.
Trump told The Wall Street Journal that the helicopter incident "wasn't a big deal" and stressed that "the pilot is fine".
However, the episode could well add further strain to efforts to broker a peace deal to end the wider Middle East war and reopen Hormuz.
Trump has repeatedly said Iran and the United States are close to an agreement, though there have been few signs of progress since a tenuous ceasefire took effect in early April.
Fighting between Israel and Iran-backed Hezbollah militants in Lebanon has continued, and Tehran has maintained its restrictions on most shipping through the Strait of Hormuz.
Washington has imposed its own blockade of Iranian ports.
with dpa
