Iranian Foreign Minister Hossein Amir-Abdollahian speaks during a press conference with his Syrian counterpart in the Iranian capital Tehran on Dec. 6, 2021. AFP
A ministry statement strongly condemned the "terrorist act" by the United States, saying it represents a "violation of the sovereignty, independence and territorial integrity of Syria".
The attack targeted "the popular groups and fighters against the occupation", said ministry spokesman Nasser Kanani, referring to US troops stationed in eastern Syria.
He denied the groups were "affiliated" with Tehran.
The comments came hours after the US military announced it had launched, on the orders of President Joe Biden, strikes on Syria targeting facilities used by groups linked to the Islamic republic.
The strikes in oil-rich Deir Ezzor province "targeted infrastructure facilities used by groups affiliated with Iran's Islamic Revolutionary Guard Corps," Central Command spokesman Colonel Joe Buccino said in a statement.
Buccino said the "precision strikes are intended to defend and protect US forces from attacks like the ones on August 15 against US personnel by Iran-backed groups," when a number of drones targeted an outpost of US-led anti-jihadist forces without causing any casualties.
Hundreds of American troops are deployed in Syria's northeast as part of a coalition focused on fighting remnants of the Islamic State group.
But Kanani called for US forces to leave Syria immediately and to "end the looting of the country's oil and grain wealth".
The strikes come as parties to the 2015 Iran nuclear deal expect Washington to give its response to a "final" draft deal presented by the European Union aimed at restoring the landmark accord.