A drone attack on a base in Jordan killed three American troops and wounded more than 30 on Sunday, with President Joe Biden blaming Iran-backed militants and vowing to hold the perpetrators to account.

It is the first time American military personnel have been killed by hostile fire in the Middle East since the war between Israel and Iran-backed Hamas began, and the incident will further raise tensions in the region and add to fears of a broader conflict directly involving Tehran.

"While we are still gathering the facts of this attack, we know it was carried out by radical Iran-backed militant groups operating in Syria and Iraq," Biden said in a statement, pledging to hold "all those responsible to account at a time and in a manner of our choosing."

Later in the day at a South Carolina church banquet hall, the president held a moment of silence for the US troops killed in the attack, then said: "We shall respond."

- 'Regional explosion' -

Hamas spokesman Sami Abu Zuhri called the attack "a message to the American administration that unless the killing of innocent people in Gaza stops, it may be faced with the entire (Muslim) nation."

"The continuation of the American-Zionist aggression on Gaza risks a regional explosion," Abu Zuhri said.

The US Central Command (CENTCOM) said Sunday evening that the attack had hit a logistics support base located at Tower 22, in northeast Jordan, and that it wounded at least 34 service members, eight of whom required evacuation from the country.

There are around 350 US Army and Air Force personnel at the base who conduct "a number of key support functions," including for the international coalition against the Islamic State jihadist group, CENTCOM said.

Jordan's government spokesman Muhannad Mubaidin, after initially claiming the attack took place in neighboring Syria, later said it "targeted an advanced position on the border with Syria."

Mubaidin condemned the attack, as did Bahrain, Egypt and Britain, whose Foreign Secretary David Cameron called on Iran to "de-escalate in the region."

- Growing Middle East crisis -

The escalating Middle East conflict poses a challenge to Biden in an election year, with various Republican politicians quick to take aim at the president over the deadly attack, including his predecessor Donald Trump, who described the situation as a "consequence of Joe Biden's weakness and surrender."

US and allied forces in Iraq and Syria have been targeted in more than 150 attacks since mid-October, according to the Pentagon, and Washington has carried out retaliatory strikes in both countries.

Many of the attacks on US personnel have been claimed by the Islamic Resistance in Iraq, a loose alliance of Iran-linked armed groups that oppose US support for Israel in the Gaza conflict.

The latest round of the Israel-Hamas conflict began when the Palestinian militant group carried out a shock attack on October 7 that resulted in about 1,140 deaths, mostly civilians, according to an AFP tally of official figures.

Following the attack, the United States rushed military aid to Israel, which has carried out a relentless military offensive that has killed at least 26,422 people in Gaza, most of them women and children, according to the Gaza health ministry.

Those deaths have sparked widespread anger across the region and stoked violence involving Iran-backed groups in Lebanon, Iraq and Syria as well as Yemen.

The Lebanon portion of the conflict has been limited to near daily exchanges of fire between Hezbollah and Israel, but American forces are directly involved in Iraq and Syria, as well as in Yemen.

The United States and Britain have both carried out strikes targeting Yemen's Iran-backed Huthi rebels, who have carried out more than two months of attacks on shipping.

The growing violence in multiple parts of the Middle East has raised fears of a broader regional conflict directly involving Iran -- a worst-case scenario that Washington is desperately seeking to avoid.