Guatemala's head of emergency evacuations, Sergio Cabanas, said the evacuees were ordered to leave 17 villages around the Volcan del Fuego, which sits about six miles south west of the colonial city of Antigua, home to 45,000 people.
The ash was blowing south-south east and authorities said the tourist centre of the country was not currently in danger, although they expected the eruption to last for hours.
Hundreds of cars, lorries and buses, blanketed with charcoal grey cash, sped away from the volcano along a two-lane paved highway towards Guatemala City. Dozens of people crammed into the backs of trucks.
Thick clouds of ash reduced visibility to less than 10 feet in the area of sugarcane fields surrounding the volcano. The elderly, women and children filled old school buses and ambulances that carried them from the area.
Authorities set up a shelter at a school in Santa Lucia, the town closest to the volcano, and by early today people had started trickling in. Most were women and children carrying blankets and going into bare classrooms.
The emergency agency said lava rolled nearly 2,000 feet down slopes billowing with ash around the Volcan del Fuego, a 12,346ft volcano whose name translates as "Volcano of Fire".
"A paroxysm of an eruption is taking place, a great volcanic eruption, with strong explosions and columns of ash," said Gustavo Chicna, a volcanologist with the National Institute of Seismology, Vulcanology, Meteorology and Hydrology. He said cinders spewing from the volcano were settling half an inch thick in some places.
He said extremely hot gases were also rolling down the sides of the volcano, which was almost entirely wreathed in ash and smoke. The emergency agency warned that flights through the area could be affected.
There was a red alert, the highest level, south and south east of the mountain. Ash was said to be landing as far as 50 miles south of the volcano.