The strike was announced by Prime Minister Haider al-Abadi in a statement and is believed to be the first of its kind by Iraqi jets on Syrian territory.
“We ordered the air force command to strike Daesh terrorist sites in Husseibeh and Albu Kamal, in Syrian territory,” the premier said, using an Arabic acronym for the jihadist organisation.
“We are determined to track down terrorists trying to kill our sons and citizens wherever they are,” he said.
Both locations cited by Abadi are very close to the border and lie in the Euphrates Valley, facing the remote western Iraqi town of Al-Qaim.
Pentagon spokesman Navy Captain Jeff Davis said the United States had provided intelligence to help the Iraqis in the strike.
“We were aware… we supported it as well with information,” Davis said, noting he thought it was the first time the Iraqi air force had hit IS inside Syria.
Husseibeh is a town in Iraq but an area that lies on the Syrian side of the border bares the same name.
Jihadists have lost most of their urban bastions in the vast western province of Anbar since Iraqi forces mounted a counter-offensive following the capture by IS of around a third of the country in 2014.
The Joint Operations Command coordinating the fight against IS in Iraq released its own statement stating that the strike took place on Friday and containing some video footage.
“Baghdad witnessed terrorist attacks using car bombs in Bayaa and Habibiyah,” the statement said, referring to bombings that killed dozens last week in the Iraqi capital.
The February 16 car bomb blast in Bayaa killed at least 52 people and was the deadliest such attack in Baghdad since a suicide truck bomb explosion in the Karrada neighbourhood set teeming shopping arcades ablaze and killed more than 320.
“After a few days of investigation, (the security forces) reached them and found their location,” the JOC said.
“This morning, the heroes of the air force attacked enemy targets with F-16s inside Syria, in the Husseibeh and Albu Kamal areas,” it said. “Their hideouts were completely destroyed.”
But they continue to move relatively easily in desert areas and have hideouts from which they harass the security forces.
An Iraqi security official speaking on condition of anonymity said it was the first time Iraqi aircraft had hunted IS targets across the border in Syria.