The US military struck two facilities in eastern Syria used by Iran's Islamic Revolutionary Guard Corps (IRGC) and affiliated groups, Defence Secretary Lloyd Austin said on Thursday.
"The 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 17 October," he said in a statement.
One US citizen contractor died from a cardiac incident during the attacks, and 21 US military personnel suffered "minor injuries, but all have since returned to duty", Austin added.
The strikes in Syria follow a direct warning earlier Thursday from President Joe Biden to Iran's supreme leader Ayatollah Ali Khamenei against the strikes on US troops, the White House said on Thursday.
"There was a direct message relayed. That's as far as I'm going to go," US National Security Council spokesman John Kirby told reporters, declining to say how it was delivered.
In his statement, Austin sought to distance the strikes against facilities used by the IRGC in Syria from the ongoing conflict between Israel and Hamas militants in Gaza.
"These narrowly tailored strikes in self-defence were intended solely to protect and defend US personnel in Iraq and Syria," he said.
"They are separate and distinct from the ongoing conflict between Israel and Hamas, and do not constitute a shift in our approach to the Israel-Hamas conflict."