Villages on the slopes of Fuego volcano were buried in volcanic ash, mud and rocks as the volcano erupted for the second time this year on Sunday.
Pyroclastic flows, which are fast-moving mixtures of very hot gas and volcanic matter, rushed down the mountainside and engulfed villages.
President Jimmy Morales has declared three days of national mourning. A further pyroclastic flow on Monday sparked alarm.
The guatemalan governement said that 1.7 million people have been affected. The death toll is expected to rise as many people that are still missing are feared to have perished, buried in the fast flowing lava flows that hit villages, killing people inside their homes.
Guatemala’s coast has also been hit by an earthquake though there are no reports of damage so far.
Sergio Cabañas, head of the country’s National Disaster Management Agency (Conred), said the town of El Rodeo had been “buried” and that the eruption that lasted over 16 hours is the worst registered in the past two years.
Temporary shelters have been set up for about 3,000 residents who have been evacuated.
Fuego is one of Latin America’s most active volcanoes. Another eruption in February this year sent ash 1.7km (1.1 mile) into the sky. Sunday’s event was on a much greater scale.
This eruption is Guatemala’s deadliest such event since 1902, when an eruption of the Santa Maria volcano killed thousands of people.