The bus was travelling on a highway in the Delaram district of Nimroz province when the blast occurred.
"This attack is one of the deadliest attacks in months," provincial governor Ghulam Dastgir Azad said.
Referring to NATO forces, Azad said "The bomb had been planted by the enemies because this morning a coalition convoy was supposed to cross the area."
Although there was no claim of responsibility, the governor blamed the attack on the Taliban, which is fighting to overthrow the Afghan government and evict nearly 150,000 foreign troops in a nearly nine-year insurgency.
According to the sources, most civilian casualties in Afghanistan are caused by Taliban attacks. Roadside bombs are the militia's main weapon.