The 7.7-magnitude quake appeared to have hit hardest in the remote Awaran region, an area that serves as a base for militants, CNN reported.
A spokesman for the National Disaster Management Authority said 330 deaths had been confirmed and more than 400 people injured. But he said the death toll is likely to rise as collapsed buildings are examined.
Officials said some of the injured were transported by air to Quetta, the provincial capital, and to Karachi.
"The dead and injured both include women and children," Provincial Home Secretary Asad Gilani told Dawn News. "Our first priority is to retrieve the bodies and shift the injured to hospitals."
Provincial government spokesman Jan Muhammad Buledi said the earthquake affected six districts -- Awaran, Kech, Gwadar, Panjgur, Chaghi and Khuzdar -- and more than 300,000 people.
Buledi said aid workers faced difficulties in contacting survivors because the earthquake heavily damaged the communication system. While teams were recovering bodies, the spokesman said the priority was to transfer move the injured to hospitals as quickly as possible.
"We are seriously lacking medical facilities and there is no space to treat injured people in the local hospitals," Buledi said. "We are trying to shift seriously injured people to Karachi through helicopters and others to the neighboring districts."
The shallow earthquake, at a depth of 9 miles, was so powerful it erected a small mountain of an island in the Arabian Sea, off Pakistan's port city of Gwadar.
The quake was felt as far away as New Delhi, capital of neighboring India.
Some of the aftershocks were measured at magnitudes as intense as 5.6.
Pakistan's News International reported Sindh and Punjab provinces also were affected by the quake but the extent of any damage in those areas was not immediately known.
CNN, quoting a police official, said the island mass created by the quake about a mile from the coast was about 30 feet high and about 100 feet in diameter.
The report quoted U.S. Geological Survey geophysicist John Bellini as saying any number of factors, including tides, may have caused the island to emerge.