Pakistani policemen guarding the heavily-fortified building were among the dead.
It is not known who carried out the attack - the fourth in Pakistan this year to apparently target foreigners or foreign interests.
No foreigners or staff at the consulate were killed in the blast but some are said to have been wounded.
The explosion, which blew a gaping hole in the mission's perimeter wall, was the second in Karachi in a matter of weeks.
It comes a day after US Defence Secretary Donald Rumsfeld had talks in Islamabad with Pakistan's President Pervez Musharraf on curbing extremism in the region.
Pakistan's information minister said the involvement of the Indian intelligence services could not be ruled out.
India has condemned the attack.
Panic
At least 40 people were injured in the blast.
Police said the bomb was concealed in a white vehicle that the driver crashed into a police kiosk at the southern end of the consulate.
It left a crater about 1.5 metres (five feet) deep, and a hole about three metres (10 feet) wide in the perimeter wall.
The force of the blast stripped leaves from trees, leaving a blanket of green on the ground, and smashed all glass panes in nearby buildings, the French news agency AFP said.
An eyewitness sitting in a large park across the street from the consulate said he heard a deafening explosion.
"There was smoke everywhere... moments later, I saw a man's body flying in the air, and he fell near me. He was badly injured. Before we could give him water or medical help, he died. It was a horrifying scene," Sharif Ajnabi told the Associated Press.
Terrified guests at the next-door Marriott luxury hotel were reported to have packed bags and rushed to check out within minutes of the bombing.
Security in the area around the consulate is very high - no cars have been allowed to park nearby since an attack in Karachi last month, although they can still drive down the street.
Al-Qaeda link
The bomb attack outside Karachi's Sheraton hotel on 8 May killed 11 French nationals and three Pakistanis.
Pakistani police suspect that attack was the work of Osama bin Laden's al-Qaeda network.
Many al-Qaeda members are believed to have fled into Pakistan after the defeat of the Taleban in neighbouring Afghanistan.
In March, a grenade attack on a church in Islamabad left five people dead, including two Americans
Many foreign diplomatic staff have left Pakistan following the attacks.
Last January General Musharraf made a televised speech to the nation in which he pledged to eradicate extremism in Pakistan.
But critics say he has made little headway in fulfilling his promise.