Witnesses said a four-wheel-drive vehicle was set ablaze in the blast on Monday and a civilian car was destroyed.
Smoke poured from the white four-wheel-drive vehicle as it burned on the central strip dividing the highway.
Bystanders said it was carrying officials and foreign security guards. US troops in armoured vehicles sealed off the area as US warplanes and helicopters flew overhead.
A US army officer near the scene said the explosion had occurred about 4km from the airport. He confirmed at least one vehicle had been hit.
There was no word on any American casualties. A US military spokesman said he had no information on the blast.
There have been several human car bomb attacks on US convoys using the main airport road in the last few days, as fighters try to show their strength in response to a planned US-led offensive against the city of Falluja.