Franca Marchesi, aged 74, was pulled from the rubble of the town's Hotel Roma on August 24th, but died on Tuesday from injuries caused in the crush.
"This is very painful news which reopens a wound that never closed," Amatrice's mayor, Sergio Pirozzi, commented. "It's difficult to explain to others, but for us the earthquake isn't just collapsed houses and a destroyed town."
He said that the only way to "do justice" to the victims was to "stay, rebuild and look forward".
Marchesi had been in hospital in a serious condition for the 82 days since the earthquake which reduced much of the mountain town to rubble.
The Hotel Roma remains under observation and the street next to it is closed to traffic. Since August, the area has been rocked by thousands of aftershocks which pose a threat to structures in an unstable condition.
Amatrice was the town worst hit by August's disaster, with 238 of the victims coming from the town.