The fatal accident occurred when the bus crashed into a bridge pillar and then fell into a ravine and caught fire.
Three people have been rescued, according to local police in the province of Baluchistan.
According to an official, there are fears that the accident was caused by the driver falling asleep, or alternatively driving far too fast.
The bus and its total of 48 passengers were traveling between the big cities of Quetta and Karachi.
Fatal road accidents are common in Pakistan as a result of poor roads, overcrowded and poorly maintained vehicles, and violations of traffic rules.
According to the World Health Organization (WHO), more than 27,000 people died on Pakistan's roads in 2018.