A US military spokesman said the mortar bomb hit the headquarters of the 101st Airborne Division in one of Saddam Hussein's palaces on Friday.
One Iraqi working at the base received minor injuries.
Mosul, in the far north of Iraq, has seen a surge in violence in recent weeks. Earlier this week, two soldiers from the 101st Airborne were shot by attackers while stuck in traffic in the centre of the city.
Their civilian vehicle was then smashed by a crowd of angry young men who attempted to burn it.
Since Washington declared major combat in Iraq over on May
1, 185 US soldiers have died in action amid a deepening insurgency.