Guatemalan emergency officials say the evacuees are leaving 17 villages around the Volcano of Fire, which sits 10 miles (16km) from the city of Antigua.
The volcano is almost always active at a low level and smoke can often be seen billowing from its crater, but large eruptions are rare.
Seismologists say explosions have also been coming from the 12,346ft-high (3,763m-high) volcano and lava has spewed 2,000ft (600m) down its slopes.
Thick clouds of ash can be seen billowing nearly two miles (3km) into the sky and rumblings were heard for several miles around.
Gustavo Chicna, a volcanologist with the National Institute of Seismology, Vulcanology, Meteorology and Hydrology, said: "A paroxysm of an eruption is taking place, a great volcanic eruption, with strong explosions and columns of ash."
He added that the cinders spewing from the volcano were settling half an inch thick in many places and that extremely hot gases coming from the volcano, which was wreathed in ash and smoke.

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