In a statement, the Pentagon said the trucks were destroyed in a single strike on Sunday near Albu Kamal, an IS-held town in Deir Ezzor province along Syria's border with Iraq.
IS controls most of the oil-rich Deir Ezzor province and part of the city, but has tried for months to seize all of the provincial capital.
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Coalition forces conducted 10 strikes in northern, central, and eastern Syria on Sunday, in one of the highest number of raids for the campaign in weeks.
The statement said 13 strikes were carried out in various parts of Iraq on Sunday as well.
A spokesperson for the coalition told AFP the strikes were not the first against IS fuel trucks, but added "it's the first time that we've hit so many at once".
The trucks had been parked at the time of the strikes, and were "getting ready to either be filled or moved to sell whatever they had in them," he said.
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IS reportedly makes millions of dollars in revenue from oil fields under its control, and the US-led coalition has regularly targeted oil infrastructure held by the group.
"Our spokesperson Colonel (Steve) Warren previously stated that we were going to start going after ISIL's financial abilities," the spokesman said.
"This strike was part of that strategy to start degrading their financial ability."
IS has declared a self-styled caliphate in swathes of territory it seized in Iraq and Syria but has faced recent setbacks from Kurdish and Arab forces in Iraq's Sinjar and parts of northeastern Syria.
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