Remarkably, there were no reports of anyone dying as a result of the 6.6-magnitude quake but more than 3,000 people were left temporarily homeless, the national civil protection agency said.
"We can confirm that we have no information on victims," said agency head Fabrizio Curcio, adding that 20 people had been injured, relatively lightly.
However "many buildings are in a critical state in historic centres and there are problems with electricity and water supplies," Curcio told reporters.
The quake struck at 7:40 am (0640 GMT) near Norcia in the region of Umbria, unleashing a shock felt in the capital Rome and even in Venice, 300 kilometres (200 miles) away.
Norcia residents were barred from returning to their homes on safety grounds and, as night fell, hundreds were being transported by bus to nearby Lake Trasimeno, where temporary accommodation in hotels and gymnasiums had been arranged.
Residents rest at a gathering point. Photo: AFP
It was Italy's biggest quake since a 6.9-magnitude one struck the south of the country in 1980, leaving 3,000 people dead.
More than 50 powerful aftershocks rumbled throughout the day, some 15 of them between magnitude 4 and 5.
Prime Minister Matteo Renzi reiterated a government pledge to rebuild every damaged house and ensure that dozens of remote communities do not become ghost towns.
"Fatigue must not turn into resignation" he urged, during a short press conference in Rome, adding that an extraordinary cabinet meeting on Monday would discuss the quake situation.
Despair sets in
The most important architectural casualty was Norcia's 14th-century Basilica of Saint Benedict.
Built on the reputed birthplace of the Catholic saint, it had survived dozens of quakes over the centuries. But it had been compromised by other recent tremors and Sunday's saw it collapse in on itself with only the facade left standing.
An aerial view of damaged Norcia. Photo: AFP
The church is looked after by an international community of Benedictine monks based in two local monasteries which attract some 50,000 pilgrims every year.
"It was like a bomb went off," said the town's deputy mayor, Pierluigi Altavilla.
"We are starting to despair. There are too many quakes now, we can't bear it anymore."
Lucia Rafael, one of several nuns forced to flee their convent in the town, told AFP the prolonged shaking had "felt like the apocalypse".
Two nuns leaving Norcia. Photo: AFP
Giuseppe Pezzanesi, mayor of Tolentino in the neighbouring Marche region, said "the people are on their knees psychologically."
Shock felt in Rome
The quake's epicentre was located at a very shallow depth of one kilometre, six kilometres north of Norcia, according to the US Geological Survey (USGS), which measured the magnitude at 6.6.
Firefighters work on a crack between two buildings. Photo: AFP
Italy's institute of geology and volcanology (IGNV) measured the quake at 6.5 and said it had been preceded by a 6.1-magnitude shock an hour earlier.
It came four days after quakes of 5.5 and 6.1 magnitude hit the same area and nine weeks after nearly 300 people died in an August 24th disaster in the tourist town of Amatrice at the peak of the holiday season.
French seismologist Pascal Bernard warned that the quakes were likely to continue in the weeks or even months to come.
"We aren't talking about replicas of this magnitude, they are normally smaller," the researcher told AFP.
A crack in one of the roads. Photo: AFP
The 13th-century civic tower in Amatrice, which was damaged but left standing by the August quake, also collapsed on Sunday.
As with Wednesday's tremors, the impact was mitigated by the fact that any buildings deemed vulnerable to seismic activity had been evacuated.
The quake was powerful enough to set off car alarms in Rome, 120 kilometres from the epicentre.
Part of the capital's underground rail network and a road flyover were temporarily closed to allow structural checks to be carried out and schools will not open Monday for the same reason.
A wall collapsed along the historic centre of Norcia. Photo: AFP
Tests were also carried out on Saint Peter's Basilica in the Vatican, which remained open to the faithful on Sunday for the Angelus prayer at which the Pope spoke of his "closeness" to the people affected.
Much of Italy's land mass and some of its surrounding waters are prone to seismic activity with the highest risk concentrated along its mountainous central spine.
Italy straddles the Eurasian and African tectonic plates, making it vulnerable to seismic activity when they move.
In addition to the Amatrice disaster in August, just over 300 people perished when a quake struck near the city of L'Aquila in 2009.
In 1980, tremors near Naples left 3,000 dead and an estimated 95,000 died in the 1908 Messina disaster, when a quake in the waters between mainland Italy and Sicily sent massive waves crashing into both coasts.