Baghdad-based Colonel Steve Warren said that over the last four days, 20 strikes in the besieged city had destroyed IS fighting positions and gun emplacements.
"We've killed more than 70 enemy fighters, including Maher Al-Bilawi, who is the commander of ISIL forces in Fallujah," Warren said, using an acronym for the IS group.
"This, of course, won't completely cause the enemy to stop fighting, but it's a blow. And it creates confusion and it causes the second-in-command to have to move up. It causes other leadership to have to move around," he added.
Iraqi forces launched an operation to recapture Fallujah, an IS stronghold located just 30 miles (50 kilometers) west of Baghdad, at the start of this week.
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Between 500 and 1,000 IS fighters hold Fallujah, and about 50,000 civilians are trapped inside the city, with the jihadists trying to kill those who attempt to flee.
US planes have dropped leaflets telling locals to avoid IS areas, Warren said.
"Those leaflets directed those who cannot leave to put white sheets on their roofs to mark their locations. The Iraqi Army is working hard to establish evacuation routes. And the local Anbar government has set up camps for displaced civilians."
Anti-government fighters seized Fallujah in early 2014, and the city later became an IS stronghold.
The jihadists overran large areas north and west of Baghdad in 2014, but have been on the defensive for months and have lost significant ground to Iraqi forces.
Warren said it was still early in the Fallujah fight, so it was unclear how long the battle would last and how much resistance IS fighters would put up.