The bus was headed to Karachi from Khyber-Pakhtunkhwa province in the north-west when it collided with the truck near Theri bypass in Sukkur district of Sindh.
At least 56 people were killed in the accident, Afzal Somoro, a police official, told PTI.
The rescue team shifted the victims to hospitals of Sukkur and Khairpur districts where emergency was declared.
A doctor from Khairpur hospital said that 21 women and 18 children were among the dead. Fifteen injured were also being treated in hospitals.
There were conflicting reports about the accident. Local media said that the driver of the bus was trying to overtake another vehicle and rammed into a truck coming from the opposite side.
However, a traffic police official said that the bus was about to take the road after getting fuel from a filling station when it hit a speeding truck.
President Mamnoon Hussain and Sindh province governor Ishratul Ebad expressed sorrow over the loss of lives and ordered an inquiry into the incident.
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