"Deaths included women and children. Eight others were wounded," he said.
Five of the wounded were in critical condition and were airlifted by Nato forces to a military hospital. Three other injured were taken to a local Kandahar hospital, he said.
Nato acknowledged the two Americans' deaths, saying they were killed in an explosion in southern Afghanistan on Friday.
The Afghan interior ministry condemned Friday's "barbaric attack by the terrorists" on the Toyota mini bus, blaming the incident on "enemies of Afghanistan" - a term often used to refer to Taliban fighters.
Deaths in Zabul
The other two civilian deaths occurred in Zabul, a province neighbouring Kandahar, when a suicide bomber dressed in a burqa detonated explosives in a shopping area of Shahjoy district, Mohammad Jan Rasoolyar, a spokesman for the provincial governor, said.
The blast also left 16 people wounded.
Kandahar is the focus of a massive build-up by US-led military forces trying to drive the Taliban from their homeland and end their bloody revolt, which began after the 2001 US-led invasion brought down their regime.
But in a sign of fresh difficulties in the war effort, General Stanley McChrystal, the top US commander in Afghanistan, acknowledged on Thursday that the campaign wouldmove more slowly than initially planned.
His forecast echoed comments by his deputy in the south, suggesting Kandahar is presenting a bigger challenge than expected, amid a shortage of Afghan security forces and scepticism among the local population.
Bombs known as improvised explosive devices (IEDs) are the weapon of choice for fighting US-led Nato forces.
Fighters plant IEDs on roadsides to inflict casualties against Afghan and foreign troops.
But usually detonated by remote control, the bombs can hit civilian vehicles.
IEDs and suicide attacks are the main cause of casualties for military forces in Afghanistan.