Many of the victims died when roofs and walls collapsed after the 5.7 magnitude quake struck in the Baluchistan province, with a power cut forcing health workers to treat the injured using flashlights.
The worst-affected area was the remote mountainous city of Harnai, where a lack of paved roads, electricity and mobile phone coverage hampered rescuers.
“We are receiving information that 20 people have been killed due to the earthquake,” Baluchistan home minister Mir Ziaullah Langau added.
A woman and six children were among 20 dead, Suhail Anwar Hashmi, a senior provincial government official, told AFP, adding that “more than 200 people have been injured.”
“We are soon sending helicopters to the area to help support the rescue operation and to evacuate injured,” Hashmi said.
Naseer Nasar, the head of Baluchistan's Provincial Disaster Management Authority, warned that the toll may rise.
The quake caused electricity to fail in the region, with health staff working until dawn without lights in a poorly equipped government hospital.
Before daybreak, “we were operating without electricity with the help of torches and mobile flashlights,” Zahoor Tarin, a senior official at the government-run Harnai hospital told AFP.
“Most of the injured came with fractured limbs. Dozens of people were sent back after first aid,” he said, adding that “at least 40 people were received with critical injuries.”
“We have imposed an emergency in the hospital and are providing them medical treatment.”
Private individuals were helping rush the injured to hospitals.
The US Geological Survey said the quake had a magnitude of 5.7 and struck around 3 am at a depth of around 20 kilometers (12 miles).
The earthquake was also felt in Baluchistan's capital Quetta.
Pakistan straddles the boundary where the Indian and Eurasian tectonic plates meet, making the country susceptible to earthquakes.
In October 2015, a 7.5-magnitude quake in Pakistan and Afghanistan killed almost 400 people across rugged terrain that impeded relief efforts.
The country was also hit by a 7.6-magnitude quake on October 8, 2005, that killed more than 73,000 people and left about 3.5 million homeless, mainly in Pakistan-controlled Kashmir.