They said nearly all of the dead were women and children travelling in a minibus which was completely destroyed.
Taliban militants have denied any responsibility for the attack.
Afghan civilians are often hit by roadside bombs used by suspected Taliban militants to target security forces and officials.
In June, Nato handed over security for the whole of Afghanistan to Afghan forces, but some 97,000 Nato troops remain.
The attack on Sunday happened in a poor and deeply traditional Pashtun area in the east of Ghazni province.
The minibus, tightly packed with people on their way to a wedding, was destroyed by a roadside bomb.
Women and children
Eight bodies were brought to a hospital, but a spokesman for the provincial governor said the number killed was far higher than that, and rescuers have been picking through the wreckage trying to count the remains.
Three men were among the dead, but the large majority of those killed and injured were women and children.
Much of the countryside of Ghazni province is in Taliban hands, and Ander district, where the attack happened, was once described by Nato as the most dangerous and unsecured area in the province, says a reporter in Kabul.
However, a Taliban spokesman said they were not responsible, and had no operations under way in that district.
The Nato-led International Security Assistance Force Isaf currently has troops from 50 contributing nations – most of them, some 68,000, from the US – providing military back-up when needed.
By the end of 2014 all combat troops should have left. They will be replaced – if approved by the Afghan government – by a smaller force that will only train and advise.