The strike -- which was condemned by the Iraqi prime minister -- is likely to fuel calls for the departure of American troops who are in the country as part of the US-led international coalition against the Islamic State (IS) jihadist group.
"It is important to note that the strike was taken in self-defense, that no civilians were harmed and that no infrastructure or facilities were struck," Pentagon spokesman Major General Pat Ryder told journalists.
It targeted a leader of Harakat al-Nujaba -- a pro-Iran armed organization in Iraq -- that was "actively involved in planning and carrying out attacks against American personnel," according to Ryder, who said it also killed another of the group's members.
Iraqi Prime Minister Mohammed Shia al-Sudani's office earlier described the strike as a "blatant aggression" as well as a "dangerous escalation and assault."
Ryder said Iraq is "an important and valued partner" and that "our forces are there at the invitation of the government of Iraq to help train and advise" as part of the anti-IS mission.
"As we have been doing all along, we will continue to consult closely with the Iraqi government about the safety and security of US forces," he said.
The strike comes amid heightened regional tensions linked to the war between US ally Israel and Iran-backed Hamas militants in the Gaza Strip.
The latest round of the Israel-Hamas conflict began when the Palestinian militant group carried out a shock cross-border attack from Gaza on October 7 that killed about 1,140 people, according to an AFP tally based on Israeli figures.
Following the attack, the United States rushed military aid to Israel, which has carried out a relentless campaign in Gaza that has killed at least 22,438 people, according to the Hamas-run territory's health ministry.
Those deaths have sparked widespread anger in the Middle East and provided an impetus for violence against American troops in the region, who have faced a spike in attacks since mid-October.
The United States has around 2,500 troops in Iraq and 900 in Syria as part of the anti-IS coalition.
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