Pope Benedict XVI sent his prayers to the victims in L'Aquila.
In a telegram to the archbishop of the city, the pope said he was praying for the "victims, especially the children," killed in the earthquake.
Civil protection department officials said up to 50,000 people may have been made homeless in some 26 cities and towns.
More than 1,500 people are believed to have been injured and thousands of houses,
churches and buildings collapsed or were damaged.
Angela Palumbo, 87, a resident of L'Aquila said: "I woke up hearing what sounded like a bomb. We managed to escape with things falling all around us.
"Everything was shaking, furniture falling. I don't remember ever seeing anything like this in my life."
Guido Bertolaso, head of Italy's public safety department, said there would be "numerous victims, many injured and so many collapsed homes," the ANSA news agency reported.
"It's an event that will mobilise the nation for many weeks."
Part of a university residence and a church tower were among the buildings that had collapsed in L'Aquila, officials said.
Television footage showed rubble blocking streets in the town and burying several parked cars.
"Police are asking people to stay away from buildings, away from lampposts, away from anything that could fall," Al Jazeera's Ayman Mohyeldin, reporting from L'Aquila, said.
"Many of these buildings are clearly showing signs of cracks, showing signs of broken windows, glass is scattered all along the streets," he said.
"There are fears that aftershocks could trigger more collapses and trap more people."
Mohyeldin said he had spoken to Ugo DePaolis, a local government official, who had told him that 60 people had died in the town of Onna, approximately 5km from L'Aquila.
Massimo Cialente, the mayor of L'Aquila, told Sky Italia television that about 100,000 people had left their homes and many buildings in L'Aquila's historic centre were damaged.
"The civil defence department is setting up some sort of tent town where they will be housed until the situation with their homes is made clearer," Sabina Castelfranco, a Rome-based journalist, told Al Jazeera.
"People are walking around draped in blankets, they have been up all night."
Antonio D'Ostilio, one resident of L'Aquila, said: "We left as soon as we felt the first tremors.
"We woke up all of a sudden and we immediately ran downstairs in our pyjamas."
Hundreds of people waited outside the town's main hospital while doctors treated people in the open air as only one operating room was functioning.
The city's university hospital was declared off limits due to concerns that it would collapse.
According to the US Geological Survey, the epicentre of the earthquake was about 95km northeast of Rome, at a depth of about 10km.
It struck 3:32am (01:32 GMT) when many people were asleep.
The earthquake was the latest and strongest in a series that have shaken the area since Sunday.
It came just hours after a magnitude 4.6 tremor shook Italy's north-central region, with no reports of damage.
Italy is criss-crossed by two fault lines, with about 20 million people at risk from earthquakes.
In October 2002, 30 people, including 27 pupils and a teacher, were crushed under a school in the tiny village of San Giuliano di Puglia during an earthquake.
Twenty-two years earlier, on November 23, 1980, a violent quake struck the southern region of Irpiona near Naples, killing 2,570, injuring 8,850 and displacing 30,000.