The quake scared residents but caused no injuries or damage, according to the civil protection agency.
The Campi Flegrei (Phlegraean Fields) is a vast volcano, though it is flat rather than cone shaped. While less well-known than nearby Vesuvius, a recent increase in activity has rattled nerves.
The quake struck at 3:35 am (0135 GMT) at a depth of around three kilometres (nearly two miles), and was felt across much of Naples.
"It was the biggest quake in the past 40 years," Mauro Di Vito, head of Italy's National Institute of Geophysics and Volcanology (INGV), told AFP.
"It is possible that there will be tremors of greater intensity" in the near future, he said.
Josi Gerardo Della Ragione, mayor of Bacoli, a coastal town on the outskirts of the southern Italian city, said it had been "the strongest of this long earthquake swarm... and among the longest".
"We have always been living on a volcanic caldera," he said, using the term for a large, cauldron-like hollow that forms after an eruption.
"We have to learn to live with this phase. Stay calm," Della Ragione told locals in a social media message.
Half a million people live on the Campi Flegrei, which last spewed lava, ashes and rocks in 1538.
The volcano's eruption 30,000 years ago is reported to have contributed to the extinction of Neanderthal man.
But the INGV said earlier this month that it believes the spike in activity could be caused by gas bubbling up, rather than magma, making "the probability of an eruption relatively low".
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