The attack came just hours before the governor of Mosul was killed in an ambush in the northern part of the country.
The Baghdad blast, a massive car bomb that detonated at a checkpoint outside the heavily fortified government compound known as the "Green Zone," was the worst attack since the handover of sovereignty to the Iraqi government three weeks ago. In addition to the Iraqi government, the Green Zone houses the offices of U.S. and British officials working in Baghdad.
"At 9:15 a.m. this morning a vehicle pulled into the search lane and tried to get into the control point and detonated," a U.S. officer said, according to Reuters.
Witnesses said the 1,000 pounds of explosives shook buildings throughout the Iraqi capital and destroyed several cars nearby, the Associated Press reported.
Among the dead were four members of the Iraqi National Guard and several civilians, a U.S. military spokesman said. One American soldier was slightly injured.
"This is naked aggression against the Iraqi people," Iraqi interim Prime Minister Iyad Allawi said, according to news reports. "We will bring these criminals to justice."
The bombing was the second such attack at an entrance of the Green Zone. In May, a suicide bomb killed Abdel-Zahraa Othman, the head of the former Iraqi Governing Council, along with nine others.
Allawi blamed the attack on militants angered by recent police raids in Baghdad that the government says has led to the capture of more than 500 suspected criminals.
Hours after the suicide attack in Baghdad, Osama Kashmoula, the governor of the northern city of Mosul, and two of his guards were killed in an ambush.
Gunmen reportedly tossed grenades at the vehicle carrying Kashmoula and opened fire with automatic weapons.
"He was on his way to Baghdad with a security escort of four cars, when the attackers in another car pulled up beside his vehicle and threw a grenade, and then shot at his car," an Iraqi Interior Ministry official, who declined to be named, told Reuters.
The killing was the second assassination in as many days. On Tuesday, a top official at the Iraqi Ministry of Industry and Minerals, Sabir Karim, was shot and killed near his home on Tuesday.
Wednesday's attacks came less than a day after Philippine officials, against the wishes of the U.S. government, announced they would withdraw their force of 51 troops from Iraq early in response to demands from kidnappers holding a Filipino national.
The kidnappers had threatened to murder truck driver Angelo de la Cruz if the Philippine government did not withdraw. In Manila, a foreign ministry official said de la Cruz has been spared.
"He is safe and there is no risk of him being executed," the official told Reuters.
Militants have also threatened to execute the second of two Bulgarian truck drivers being held hostage in Baghdad. Though Arab news reports say the kidnappers, led by Islamist Abu Musab al-Zarqawi, have beheaded one of the two men -- Georgi Lazov, according to Bulgarian media reports -- Bulgarian officials have refused to withdraw their 470 troops.