A rocket that landed within several hundred yards of US troops at Qayyarah air base near Mosul may have contained mustard agent, it said.
No-one was hurt in Tuesday's attack on the base, which is home to several hundred US soldiers.
If confirmed, it would be the first chemical weapons attack on coalition forces in Iraq.
Troops stationed at the base are equipped to deal with chemical attacks.
"On September 20, mid-afternoon Iraq time, the Iraqi air base at [Qayyarah] West came under attack by indirect fire," the Pentagon said in a statement.
"An initial test of the remnants of the weapon used returned a positive test for a mustard agent.  The device, likely a rocket or mortar, was imprecise and crude."
Following decontamination, no service personnel showed signs or symptoms of mustard exposure, the Pentagon said.
"This attack has not impacted our mission in any way, nor have we changed our security posture in the area around [the base]," the statement added.
"We train and equip ourselves and our partners for just this type of eventuality."
There was no immediate confirmation of the attack in Baghdad, Quentin Sommerville, the BBC's Middle East correspondent, reports.
However, there have been 20 documented cases of chemical weapons being used against Kurdish fighters in Iraq and a quarter of those cases involved mustard gas.
IS has long been suspected of making and using crude chemical weapons in Iraq and Syria, where it also controls territory.
Mustard agent in sufficient quantities can maim or kill by damaging skin, eyes and airways.
Mosul, Iraq's second largest city, has been under IS control for the past two years and the battle to retake it is expected to begin in the coming weeks.
US troops are providing assistance to local forces as they prepare for the offensive.
Islamic State militants may have fired a chemical rocket at American troops based in Iraq, the US military says.