Seven precision-guided missiles were fired at heavily armed fighters who were stopping and searching civilian cars at gunpoint near Karabilah, close to the volatile town of Qaim, the US marines said in a statement on Saturday.
The fighters were armed with AK-47 assault rifles, medium machine guns and rocket-propelled grenade launchers and had "set up a barricade on a main road to the city and were threatening Iraqi civilians," the military said.
US warplanes backed by helicopters launched air strikes that began at 11:40 am (local time) and ended at 4 pm "once all the targets were destroyed", the military said.
Approximately 40 fighters were killed and there were no marines casualties.
"The coalition aircraft and fighter jets and attack helicopters from the 2nd Marine Aircraft Wing attacked the insurgent compound and surrounding area targeting the armed men," the statement said.
"There are no reports of civilian casualties or collateral damage."
It was unclear if there were any foreign fighters among the killed. The region is known as a haven for Islamic fighters crossing in and out of Iraq across the Syrian border to attack US and Iraqi security forces.
"The coalition aircraft and fighter jets and attack helicopters from the 2nd Marine Aircraft Wing attacked the insurgent compound and surrounding area targeting the armed men"
US military statement
The US military launched two major counter-insurgent offensives in the area last month that killed an estimated 140 fighters.
Since Thursday, attacks by anti-US fighters in Iraq's volatile al-Anbar province have claimed the lives of seven marines.
The bodies of 21 slain Iraqi men, some beheaded and most shot execution style, were found on Friday in three separate locations near Qaim.
It is feared the bodies may belong to about 20 Iraqi soldiers who went missing on Wednesday after leaving a military base bound for a vacation in Baghdad.
At least 1693 US soldiers have died since the Iraq war began in March 2003, according to an Associated Press count.