The blast at the Shah Noorani shrine occurred while hundreds of people were inside, local district commissioner Hashim Ghalzai told Reuters.
Provincial Home Minister Sarfaraz Bugti said 52 people were killed and that more than 105, including many women and children, were wounded.
The shrine is located in Baluchistan province about 100 km (60 miles) north of the port city of Karachi, to where rescue official Hakeem Nasi told Geo TV dozens of wounded were being moved.
The government dispatched 25 ambulances from the nearby town of Hub to the shrine, said Akbar Harifal, provincial home secretary for Baluchistan. The army was called in to assist with rescue operations, given the remoteness of the site, Bugti said.
It was not clear whether the attack was carried out by a suicide bomber or a planted device, according to Bugti.
The province has seen some of the worst militant attacks this year in Pakistan.
Islamic State said in a statement via its Amaq news agency that its fighters had carried out Saturday's bombing.
The jihadist group also claimed responsibility for the last major attack in the province, at a police academy last month, that killed around 60 people.
Muslim shrines have often been targeted by militant groups, many of whom adhere to a strict interpretation of Islam that regards veneration of saints at shrines such as Shah Noorani as heresy.
Baluchistan is also a key link in a US$46 billion transport and trade corridor between Pakistan and China, which hinges on a deep-water port in the southwestern city of Gwadar.