Police officials said the death toll could be over 300, Pakistan's NNI news agency reported.
The accident occurred at about 4 am when a train sitting in a station near Ghotki, in southern Sindh province, was rear-ended by a second train, Abdul Aziz, a senior controller at Pakistan Railways, said.
Aziz said the collision caused several cars to derail and spill over onto another track, where they were struck by the third train, causing further derailment.
"It is a very gruesome situation," local police official Aga Mohammed Tahir told The Associated Press.
"Rescue workers have started to pull the dead and injured out. There were many people inside and there are a lot of casualties."
Tahir said that "dozens" of people had been killed or injured, but that no exact figures would be possible for some time.
He said at least 13 train cars derailed, and that the injured were being taken in ambulances and cars to area hospitals.
"They are being pulled out every minute," he said.
Ghotki is about 600 km northeast of Karachi, in remote Sindh province.
A second railway official, Sajjad Ahmed, said the train in the station was the Quetta Express, which was bringing passengers from the eastern city of Lahore to the southwestern city of Quetta, when it developed a technical problem.
Technicians were working on the train when it was hit by the Karachi Express, a night-coach passenger train bringing people from Lahore to the southern port city of Karachi.
The impact pushed three carriages onto an adjacent track, and they in turn were hit by the oncoming Tezgam Express, which was bringing people from Karachi north to Rawalpindi, near the capital.
Pakistan's railways are antiquated, and dozens of people have been killed in train accidents in recent years.
On March 5, five people were killed and 25 injured when a passenger train derailed in eastern Punjab province.
On September 20, 2003, a train ploughed into a packed bus in central Pakistan, killing at least 27 people and injuring six others.
Accidents are often blamed on faulty equipment or human error.
WITH PTI INPUTS