The quake struck in the sea at a depth of 133 kilometres some 48 kilometres northwest of the US territory's capital Hagatna.
"A destructive tsunami was not generated because this earthquake is located too deep inside the earth," the Pacific Tsunami Warning Centre said.
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The largest quake in recent years hit in 1993. Although no one died in the 7.7-magnitude tremor, several people were injured and buildings suffered structural damage.
Geoscience Australia said today's quake, which it estimated at a magnitude of 6.6, was not shallow enough to have generated a tsunami.
"It gave Guam a good shake but not enough to do much damage, no damage likely," seismologist Daniel Jaksa told AFP.
Jaksa added that the Guam tremor hit about three minutes after a 6.0 magnitude quake struck off the Pacific nation of Vanuatu but the two were unrelated.
The Vanuatu quake, estimated at a depth of more than 200 kilometres, hit offshore about 150 kilometres north of the capital Port Vila but was not expected to trigger a tsunami.
"There's nothing unusual about earthquakes in this region," he said.
Vanuatu lies on the so-called "Pacific Ring of Fire", a zone of frequent seismic activity caused by friction between shifting tectonic plates.
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