There is no immediate report of casualties after the eruption started overnight.
The 3763-metre-high volcano is one of the most active in Central America.
It last erupted in June 2023.
The volcano spewed gas and ash up to seven kilometres into the sky on Monday, leading authorities to close schools in the vicinity and a key road connecting communities.
The biggest danger from the volcano are lahars, a mixture of ash, rock, mud and debris, that can bury entire towns.
A 2018 eruption killed 194 people and left another 234 missing.
Isaac García, 43, a resident of El Porvenir on the slopes of the volcano, had that tragedy in mind when he and his family decided to heed authorities' warnings to leave early on Monday.
"We were a little worried because a few years ago the volcano became active," García said, referring to the 2018 eruption, as he spoke with a mask to protect against the falling ash.
He came to a shelter opened in San Juan Alotenango with his mother, wife and their three children as well as other relatives.
The volcano is 53km from Guatemala's capital.
The flow of volcanic material is weak to moderate but expected to increase, Guatemala's disaster agency said.
with DPA
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