The strikes came hours after two new attacks on US forces in Syria and Iraq.
President Joe Biden this week warned Iran's supreme leader Ayatollah Ali Khamenei that the US would respond to additional attacks. Pentagon press secretary Brig Gen Pat Ryder said on Thursday that any response would come “at a time and place of our choosing”.
A US defence official told The National that the strikes, using precision munitions, were deemed to have been successful. They came hours after two previously unreported attacks on US forces in Iraq and Syria, a second defence official said.
Mr Biden ordered the US strikes, which the Pentagon said took out weapons and munitions storage centres connected to the IRGC.
“These precision self-defence strikes are a response to a series of ongoing and mostly unsuccessful attacks against US personnel in Iraq and Syria by Iranian-backed militia groups that began on October 17,” US Defence Secretary Lloyd Austin said in a statement.
“These Iranian-backed attacks against US forces are unacceptable and must stop.”
Brig Gen Ryder said an F-16 and an F-15 had conducted the “self-defence” strikes that destroyed weapons and ammunition storage facilities.
At least 21 US personnel have experienced “minor injuries” in rocket and drone attacks in Iraq and Syria since October 17, the Pentagon said.
Within hours of the Pentagon briefing, US troops were attacked again, once in Syria and once in Iraq, the second defence official told The National. There were no immediate reports of injuries.
“There have been more attacks unfortunately,” the official said.
The the precision strikes took place at about 4.30am on Friday in Syria (5.30am UAE time) near Abu Kamal, a Syrian town on the border with Iraq.
“The purpose of those two sites that we targeted was to have a significant impact on future IRGC and Iran-backed militia group operations,” White House National Security spokesman John Kirby told reporters.
“It went right at storage facilities and ammo depots that we know will be used to support the work of these militia groups and particularly in Syria.”
Joe Biden warns Iran: 'Be careful' - video
The senior US military official said there had been Iranian-aligned militia and IRGC personnel on the base and no civilians.
Mr Austin emphasised that the US is not seeking to expand conflict or engage in further hostilities.
But “if attacks by Iran's proxies against US forces continue, we will not hesitate to take further necessary measures to protect our people”.
The US is trying to contain the Israel-Gaza war to stop it from escalating into a regional conflict.
The strikes were “separate and distinct from the ongoing conflict between Israel and Hamas, and do not constitute a shift in the US approach to the Israel-Hamas conflict”, Brig Gen Ryder said.
As regional tension soars, US and coalition troops have been attacked at least 14 times in Iraq and six times in Syria, Brig Gen Ryder said.
“Most of these attacks were disrupted by defensive measures and failed to reach their targets,” he noted.
The 21 US forces members who suffered injuries have all returned to duty, the Pentagon said. A contractor died of a heart attack while seeking shelter.
Richard Goldberg, a senior adviser at the Foundation for Defence of Democracies, said the Biden administration had played down Iran's role in the October 7 Hamas attack in an attempt to preserve the possibility of a new nuclear deal with Tehran.
“Iran will always escalate until they perceive that doing so will lead to a direct military confrontation with the United States – something they avoid at all cost,” Mr Goldberg told The National.
“To deter Iran, you can't turn the other cheek – that only invites escalation and miscalculation in Tehran.”
He described the US strikes as “the least escalatory response on the menu of options” available to Mr Biden.
Warships and troops sent to region
The US has sent more warships and fighter jets to the region over the past three weeks.
On Thursday, the Pentagon said about 900 more American troops had arrived in the Middle East or were heading there to bolster air defences for US personnel.
Israel said on Friday that military raids into Gaza were in preparation for “the next stage of the operation” as fears grew that a ground invasion of the Palestinian enclave could spark a wider Middle East conflict.
Prime Minister Benjamin Netanyahu's government has bombarded the densely populated Gaza Strip since the October 7 Hamas attack on Israeli communities.
The militant group killed about 1,400 people including children and took more than 200 hostages, some of them infants and older adults.
The Hamas-controlled Gaza Health Ministry said on Thursday that more than 7,000 Palestinians had been killed in the retaliatory air strikes, including about 3,000 children.
A missile launched during fighting between Hamas and Israel struck an Egyptian resort town about 220km from the Gaza Strip early on Friday, Al Qahera News reported.
The missile hit a medical centre in Taba, wounding at least six people, according to the report.