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Some 20 troops and an Iraqi civilian were injured in the attack, which happened in the volatile province of Diyala, to the north-east of Baghdad.
There has been fierce fighting in Diyala recently, pitting US and Iraqi forces against Sunni and Shia militias.
It is thought to be the worst single US loss on the ground since late 2005, when 10 marines died near Falluja.
In January 2007, 12 US soldiers died when a Black Hawk military helicopter crashed near Baghdad.
More than 3,300 US troops have been killed and some 24,300 have been injured in Iraq since the conflict began.
In Baghdad, meanwhile, two car bombs exploded on Tuesday morning near the Iranian embassy, police and witnesses said. At least four people were reported hurt in the blasts.
Two blasts in the same area on Monday left one person dead.