Major Quentin Innis, a Canadian military spokesman, told Reuters that five Afghans were missing after the aircraft ploughed into their mud-walled homes close to a military airfield in Lashkar Gah, the capital of Helmand province, on Monday.
The plane had been coming in to land when a truck crossed the runway, forcing the pilot into a fatal change of course, he said.
"The latest information we have ... shows a total of five people have been killed, two on the plane and three on the ground," he said.
Eight foreign nationals were injured on board the plane, he added, declining to give nationalities.
Several of them were Americans who suffered minor injuries, according to Lou Fintor, a spokesman for the US embassy in Kabul, adding that the plane was being used by anti-narcotics agents.
He had no other details.
Sabotage ruled out
Helmand has borne the brunt of a growing insurgency by Taliban fighters, and it is Afghanistan's main drug producing region, but several officials ruled out any chance that the aircraft had been fired on or sabotaged.
Minutes after the crash, foreign troops cordoned off the site as ambulances took the injured out.
John Reid was due to meet British
troops stationed in Helmand
One helicopter was seen ferrying casualties to a military base for US-led forces.
John Reid, the British defence secretary, was due to visit British troops stationed in Helmand on Monday, but was making a stopover in Kandahar when the cargo plane crashed.
His travel plans were thrown into some doubt as one of the planes being used for his visit had been seconded to help with the emergency in Lashkar Gah, officials said.
Last year, a Pakistani cargo plane, carrying supplies for the US-led forces hit a mountain close to the US military base at Bagram, north of Kabul, killing all eight people on board.
The cause of that crash was said to have been bad weather.
A year earlier, 104 passengers, including the crew of a private plane, were killed after it hit a mountain during stormy weather south of the capital.