The estimate from the Syrian Observatory for Human Rights came nine days into an all-out army assault on the rebel-held Khaldiyeh and Old City neighbourhoods, which have been under siege for more than a year.
Today, regime forces subjected insurgent areas of the city to fierce shelling, said the Observatory.
"Sixty to 70 percent of buildings in Khaldiyeh are either totally destroyed, partially destroyed, or unsuitable for habitation," Observatory director Rami Abdel Rahman told AFP.
"Of all Syria's cities, Homs has suffered the highest levels of destruction... Images of Homs make it look like a world war has hit the city. Much of it has been flattened," he added.
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Amateur video posted online by activists today showed flames and thick black smoke rising from several empty burnt-out buildings already riddled with holes.
Some structures shown in the video are barely standing.
"Even if the regime takes the neighbourhoods back, there's barely a house left standing to return to," said Abdel Rahman.
Today, government troops used mortars, rocket fire and heavy artillery to target rebel areas in the city, the Britain-based Observatory said.
On the edges of Khaldiyeh, fresh clashes broke out between rebels and troops and pro-regime militiamen, it added.
According to the United Nations, some 2,500 to 4,000 people are trapped in the besieged areas.
In Damascus, regime warplanes targeted Jubar in the east of the capital, while tanks hit Qaboon in the northeast, said the Observatory.
In northern Damascus, the army tried to storm Barzeh, where rebels are still holed up, the watchdog said.
Syria's 27-month war has killed more than 100,000 people, the Observatory estimates.