The accident took place in Khanpur area of Rahim Yar Khan, some 600 kms from here around 6 am, media reports said.
One of the buses was en route to Bahawalpur from Faisalabad while the other was heading from Karachi to Rahim Yar Khan, rescue services spokesperson Deeba Shahnaz said.
The incident occurred due to overspeeding and claimed the lives of at least 30 people besides leaving over 55 people injured, rescue officials said.
Those injured have been shifted to hospitals in Khanpur and Rahim Yar Khan hospitals. Condition of some injured persons is stated to be serious, Radio Pakistan reported.
Prime Minister Nawaz Sharif expressed grief and sorrow over the loss of precious lives in the accident and directed the authorities concerned to provide best medical treatment to the injured, it said.