A senior police source said the ambush on Tuesday occurred near the town of Salman Pak, about 30km southeast of the Iraqi capital and left the highway "littered with bodies ... fighting is still going on".
Iraq's interior ministry and the US military had no immediate information on the 10-vehicle convoy attack, but the area around Salman Pak has been a focal point of activity against US-led forces over the past year.
The ambush came just hours after a US soldier and an Iraqi national guardsman were reported killed and others injured in a car bomb that rocked the Green Zone in Baghdad, journalists and hospital sources said.
Green Zone attack
Ziyad al-Samarrai, an Iraqi journalist, told Aljazeera from Baghdad: "A US soldier and an Iraqi National Guard were killed in the explosion on Tuesday."
A US military spokesman, however, said no US personnel were hurt. The blast comes a day after a similar strike at the Green Zone's western gate.
Iraqis working with US forces are
routinely attacked in Baghdad
Hospital officials have confirmed that at least 13 people have been injured, al-Samarrai said.
"All roads leading to the site have been closed off by US forces, preventing reporters from approaching it," said al-Samarrai.
"US forces, Iraqi police and the national guards cannot control such attacks any longer, particularly the suicide operations targeting them. They cannot even face these attacks. They only set up checkpoints."
According to al-Samarrai, "Such attacks take place almost daily. Iraqi resistance fighters are able to turn the country into a battlefield whenever they want to."
The blast, which sent a large plume of smoke over the city, occurred at a different entrance to the zone than that targeted on Monday, where a car bomb killed seven Iraqis and injured 19.
A national guard officer said there were many wounded in Tuesday's blast, which occurred at 8.20am (0520 GMT).
At least 13 of the wounded, most of them in a serious condition, were taken to Baghdad's Yarmuk hospital, according to Dr Raad Abd al-Jabbar.
"There's been a VBIED [vehicle-based improvised explosive device] at Checkpoint 12," the spokesman said.
"Iraqi resistance fighters are able to turn the country into a battlefield whenever they want to"
"I saw a Kia car drive through the checkpoint and it exploded," said bus driver Muhammad Kadhim as he lay wounded at the civilian Yarmuk hospital.
"I'm sure two National Guards next to it were killed," he added, although the US spokesman said he knew of no Iraqi military casualties.
"Two of the people standing next to me were killed. I saw them cut to pieces," said another wounded man, Firas Sahir, a labourer who was lining up to go into work in the Green Zone.
Isan Nasir, an official who keeps patient records at Yarmuk hospital, said 12 people, all men, had been brought in wounded and there were no dead bodies at the hospital, though that might change.
Monday's explosion occurred when an attacker detonated his car as he was waiting for his vehicle to be searched at a checkpoint, Iraqi national guards said.
Two mortar rounds landed in the Green Zone, which houses the interim Iraqi government and embassies, later the same day.
And on 4 December a car bomb exploded at a police station outside one of the zone's main entrances.