The national disaster agency says officials were carrying out "a massive evacuation of thousands of people" in 17 villages.
Sergio Cabanas says this includes some 33,000 people around the Volcano of Fire, which sits about 10 miles from the colonial city of Antigua.
Lava from the volcano reportedly spewed nearly 2,000 feet down two slopes, while billowing ash shot 3,000 feet into the air on Thursday.
Seismologists confirmed explosions have been coming from the 12,346-foot-high volcano.
There was a general orange alert, the second-highest level, but a red alert south and southeast of the mountain, where, Gustavo Chicna, a volcanologist said, “it's almost in total darkness.”
Teresa Marroquin, disaster coordinator for the Guatemalan Red Cross, said the organization had set up 10 emergency shelters and was sending hygiene kits and water.
“There are lots of respiratory problems and eye problems,” Marroquin said.
The Volcano of Fire is one of the most active volcanoes in the world. Smoke pours from its top daily, but large eruptions like the one today are somewhat rare.
One scientist in Guatemala said today's eruption was the biggest since 1999 with this being the sixth eruption of the volcano so far this year.