The US military's Central Command said an Iran-backed militia targeted the Al Asad airbase, which hosts American troops, with ballistic missiles and rockets on Saturday evening.
An unspecified number of US personnel were "undergoing evaluation for traumatic brain injuries".
At least one Iraqi service member was wounded in the attack.
The strike against the base was claimed by a group calling itself the Islamic Resistance in Iraq. According to the US-based Washington Institute for Near East Policy, the group emerged in late 2023 and is comprised of several Iran-affiliated armed groups operating in Iraq.
It has claimed other attacks against US forces in recent weeks. And Al Asad base has been attacked repeatedly in recent years.
The US military said most of the missiles fired on Saturday were intercepted but some evaded air defences and hit the base, adding that an assessment of the damage is ongoing.
It is the latest in a series of attacks on US positions in Iraq and Syria by Iran's proxies in the region since the outbreak of the Israel-Gaza conflict last October.
Understanding a week of missile strikes across Middle East
The US military and allies have also intervened to stop Houthi missile attacks on international shipping in the Red Sea.
US forces carried out another airstrike on Saturday against the Houthis - an Iran-backed rebel group controlling much of western Yemen. The US military said it targeted a launch site, after identifying an anti-ship missile "that was aimed into the Gulf of Aden and prepared to launch".
Red Sea 'scary' for ships' crews, says captain
The Iranian military has carried out a number of missile strikes in recent days against targets in Syria, Iraq and Pakistan.
Earlier on Saturday, Iran accused Israel of carrying out an airstrike in the Syrian capital Damascus which killed five senior members of Iran's security forces.
By Sean Seddon