President Joe Biden said on Sunday that the US “shall respond” after three American troops were killed and dozens more were injured in an overnight drone strike in northeast Jordan near the Syrian border.

Biden blamed Iran-backed militias for the first US fatalities after months of strikes by such groups against American forces across the Middle East since the start of the Israel-Hamas war.

Biden, who was travelling in South Carolina, asked for a moment of silence during an appearance at a Baptist church's banquet hall.

“We had a tough day last night in the Middle East. We lost three brave souls in an attack on one of our bases," he said. After the moment of silence, Biden added, “and we shall respond”.

With an increasing risk of military escalation in the region, US officials were working to conclusively identify the precise group responsible for the attack, but they have assessed that one of several Iranian-backed groups was behind it.

Biden said in a written statement that the United States “will hold all those responsible to account at a time and in a manner (of) our choosing”. Defence Secretary Lloyd Austin said "we will take all necessary actions to defend the United States, our troops, and our interests”.

Iran-backed fighters in east Syria began evacuating their posts, fearing US airstrikes, according to Omar Abu Layla, a Europe-based activist who heads the Deir Ezzor 24 media outlet. He told The Associated Press that the areas are the strongholds of Mayadeen and Boukamal.

US Central Command said at least 34 troops were injured by the one-way attack drone, with eight flown out of Jordan for follow-up care. It described the eight as being in stable condition.

The large drone struck a logistics support base in Jordan known as Tower 22. It is along the Syrian border and is used largely by troops involved in the advise-and-assist mission for Jordanian forces.

Central Command said approximately 350 US Army and Air Force personnel were deployed to the base. The three who were killed and most of the wounded were Army soldiers, according to several US officials, who spoke on condition of anonymity to give details not yet made public.

The small installation, which Jordan does not publicly disclose, includes US engineering, aviation, logistics and security troops. Austin said the troops were deployed there “to work for the lasting defeat of ISIS”.

Three officials said the drone struck near the troops' sleeping quarters, which they said explained the high casualty count.

The US military base at al-Tanf in Syria is just 20 kilometers (12 miles) north of Tower 22. The Jordanian installation provides a critical logistical hub for US forces in Syria, including those at al-Tanf, which is near where the borders of Iraq, Syria and Jordan intersect.

In a statement on Jordan's state-run Petra news agency, the country “condemned the terrorist attack” that targeted the US troops.

That report described the drone strike as targeting “an outpost on the border with Syria” and said it did not wound any Jordanian troops.

“Jordan will continue to counter terrorism and the smuggling of drugs and weapons across the Syrian border into Jordan, and will confront with firmness and determination anyone who attempts to attack the security of the kingdom,” the statement attributed to Muhannad Mubaidin, a government spokesman, said.

US troops long have used Jordan, a kingdom bordering Iraq, Israel, the Palestinian territory of the West Bank, Saudi Arabia and Syria, as a basing point. Some 3,000 American troops typically are stationed across Jordan.

Since the war in Gaza began October 7, Iranian-backed militias have struck American military installations in Iraq more than 60 times and in Syria more than 90 times, with a mix of drones, rockets, mortars and ballistic missiles.

The attack on Sunday was the first targeting American troops in Jordan during the Israel-Hamas war and the first to result in the loss of American lives. Scores of US personnel have been wounded, including some with traumatic brain injuries, during the attacks.

The militias have said that their strikes are in retaliation for Washington's support for Israel in the war in Gaza and that they aim to push US forces out of the region.

The US in recent months has struck targets in Iraq, Syria and Yemen to respond to attacks on American forces in the region and to deter Iran-backed Houthi rebels from continuing to threaten commercial shipping in the Red Sea.

“I am confident the Biden Administration will respond in a deliberate and proportional manner,” said Sen. Jack Reed, D-R.I., who heads the Senate Armed Services Committee.

Republicans in Congress said the administration's approach had failed to deter America's adversaries in the region.

“We need a major reset of our Middle East policy to protect our national security interests,” said Republican Rep. Michael McCaul of Texas, chairman of the House Foreign Affairs Committee. Sen. Lindsay Graham, R-S.C., went further, urging the administration “to strike targets of significance inside Iran, not only as reprisal for the killing of our forces, but as deterrence against future aggression. The only thing the Iranian regime understands is force”.

Biden, who was in Columbia, South Carolina, on Sunday, was briefed in the morning by Austin, national security adviser Jake Sullivan, and principal deputy national security adviser Jon Finer, White House press secretary Karine Jean-Pierre said. In the afternoon, he met virtually with Vice President Kamala Harris and his national security team for an update.

The president, in the written statement, called it a “despicable and wholly unjust attack” and said the service members were “risking their own safety for the safety of their fellow Americans, and our allies and partners with whom we stand in the fight against terrorism. It is a fight we will not cease”.

Syria is still in the midst of a civil war and long has been a launch pad for Iranian-backed forces there, including the Lebanese militia Hezbollah. Iraq has multiple Iranian-backed Shiite militias operating there as well.

Jordan, a staunch Western ally and a crucial power in Jerusalem for its oversight of holy sites there, is suspected of launching airstrikes in Syria to disrupt drug smugglers, including one that killed nine people earlier this month.

An umbrella group for Iran-backed factions known as the Islamic Resistance in Iraq earlier claimed launching explosive drone attacks targeting three areas in Syria, as well as one inside of “occupied Palestine”.

The group has claimed responsibility for dozens of attacks against bases housing US troops in Iraq and Syria since the Israel-Hamas war began.

Three officials with Iran-backed militias in Iraq, who spoke on condition of anonymity because they were not authorised to discuss the matter with journalists, said the drone attack against the base in Jordan was launched by one of the Iraqi groups. No faction has yet officially claimed responsibility.

Officials said the US military is not tracking any other attacks on its forces Sunday in the region.