The quake brought down numerous buildings across central Italy on Sunday and emergency services were checking to see if there were any casualties, civil protection authorities said.
It measured 7.1 according to an initial estimate by the US Geological Survey and was later revised to 6.6, the biggest since almost 300 people were killed in central Italy on Aug 24 by a quake that levelled several small towns.
While there were no immediate reports of casualties on Sunday, damage was substantial.
Live television coverage showed the collapse of a church in the centre of Norcia, a town near Perugia in Umbria. Parts of the town had already been sealed off.
Sunday's earthquake followed a series of tremors to strike the country in the past five days.
It was felt as far north as Bolzano, near the border with Austria and as far south as the Puglia region at the southern tip of the Italian peninsula and was felt strongly in the capital Rome.
A series of strong earthquakes struck the area on Wednesday.