The volcano is about 25 miles southwest of the country's capital. This is the second time this year it has erupted.
Sunday's eruption shot thick clouds of smoke and ash into the air and sent a river of lava flowing into several towns.
As of Monday afternoon, Guatemala's national emergency response agency said more than 3,200 people had been evacuated with more than 1.7 million people affected. Rescue and response operations are ongoing.
Officials are warning about the possibility of pyroclastic flows and lahars, which are both streams of volcanic matter that are fast moving and very dangerous.
Guatemala's President Jimmy Morales has announced three days of national mourning.
Additional reporting from Newsy affiliate CNN.