The attack brings to more than 30 the number of people now killed in a violent backlash over a YouTube trailer for the film, believed to have been produced by a small group of extremist Christians.
Security officials said nine foreigners were among those killed on a major highway leading to Kabul airport and close to a wedding hall when the bomber blew her station wagon up alongside a minivan carrying foreign workers.
An AFP photographer saw at least six bodies lying among the wreckage of a gutted minivan, and another vehicle destroyed by flames still burning in the middle of the highway, with debris flung all around.
Hezb-i-Islami, the second largest insurgent group after the Taliban who have been fighting US-led troops and the government for 10 years, claimed the attack.
"The bombing was carried out by a woman named Fatima. The bombing was in retaliation for the insult to our Prophet," spokesman Zubair Sidiqi told AFP in a telephone from an undisclosed location. It is extremely rare for the faction to claim a suicide attack in Afghanistan.
It is also rare for women to carry out suicide attacks. Taliban fighters last week stormed a British-run airfield, killing two US Marines and destroying six US fighter jets also to avenge the film.
A week of furious protests outside US embassies and other American symbols in at least 20 countries have killed 19 other people, including the American ambassador to Libya and three other US diplomats in the North African country.