Sean McCormack, a US state department spokesman, said: “There were no American diplomats or American citizens in the car at the time.”
He said the driver of the US vehicle was slightly injured.
The latest attack comes as George Bush, the US president is on a week-long tour of the Middle East.
Rula Amin, Al Jazeera’s correspondent at the scene, said it was impossible to even identify the licence plates of one of the cars.
Amin said it was a significant political development given the attack had apparently been launched on an American target.
Secretary of State Condoleezza Rice called the bombing a “terrorist attack”.
“The United States will, of course, not be deterred in its efforts to help the Lebanese people, to help the democratic forces in Lebanon, to help Lebanon resist force and interference in their affairs,” she told reporters in the Saudi capital, Riyadh.
There has been a series of bombings in Lebanon during the past year, most of which have targeted prominent Christian politicians all perceived to be anti-Syrian.
US diplomatic and military missions in Lebanon were attacked on a number of occasions during the country’s civil war betwen 1975 and 1990.
Soldiers and investigators were at the bomb scene which was cordoned off.
Amin said the blast took place in a busy neighbourhood at a time when many people were returning home from work.
Ahmad Fatfat, the Lebanese youth minister, said the blast was aimed at foiling an initiative by the Arab League to bring an end to the political deadlock in Lebanon.
Lebanon is in the middle of a political crisis with the government and opposition failing to reach an agreement to name a new president.
The post has been vacant since the end of November when the term of Emile Lahoud ended.
A parliamentary vote to name his successor has been postponed 12 times.
Amr Mussa, the head of the Arab League, was scheduled to arrive in Beirut on Wednesday after an initial visit last week made little headway.
Fatfat said the US vehicle had just dropped several American diplomats at Beirut airport and was apparently heading back to the embassy when the attack occurred.