Many of the dead were in Accumoli, close to the epicentre, and a short distance away in Amatrice, which was largely reduced to rubble.
The village of Pescara del Tronto was levelled to the ground and the number of dead was expected to rise.
The quake hit at 03:36 (01:36 GMT), 100km (65 miles) north-east of Rome.
Prime Minister Matteo Renzi paid tribute to the volunteers and civil defence officials who had rushed to the scene in the middle of the night and used their bare hands to dig for survivors.
The quake struck at a shallow depth of 10km and its intensity was compared to that of the Aquila earthquake in April 2009 in which 309 people died.
Some buildings in the capital shook for 20 seconds as the quake struck the regional border area of Umbria, Lazio and Le Marche. It was felt from Bologna in the north to Naples in the south. Some 80 aftershocks have been reported since.
Local authorities were unsure of the full extent of casualties but 28 deaths were reported in Accumoli and Amatrice.
At least 11 people were reported dead including children in the neighbouring villages of Arquata del Tronto and Pescara del Tronto. Hundreds of people were injured across the region, officials said.
The mayor of Arquata del Tronto, Aleandro Petrucci, spoke of a disaster. “The village isn’t there anymore. Almost all the houses in Pescara del Tronto have collapsed.”
An elderly couple and a boy were among the victims there while 20 people have been taken to hospital. Two boys aged four and seven were pulled alive from the rubble of the house they had been staying in with their grandmother, Ansa news agency reports. Rescuers said they had been sheltering under a bed.
Rescuers were still trying to reach the remote village of Peracchia di Acqua Santa Terme a few kilometres to the east.