The two buses, carrying around 100 passengers, collided on Monday in the town of Khanpur in Rahim Yar Khan district, about 800km south of the capital Islamabad.
Jamshid Shah, a police official, said speeding seemed to be the cause of the accident, which occurred on a dangerous curve.
One of the buses was on its way from Karachi to Lahore while the other was heading to Sadiqabad from Faisalabad, Al Jazeera reported.
Shah says women and children are among those who were killed and injured. He says police and rescue officials are using cutters to retrieve bodies stuck inside the two buses.
Mehar Arsal, a local police chief, said the buses slammed into trees after colliding with each other.
Pakistan has a dismal record of fatal traffic accidents due to poor roads, badly maintained vehicles and reckless driving.
More than 4,600 people were killed in road traffic accidents in 2013, the last year the government released official data.