Authorities said at least six people were dead or missing following the eruption.
A search was underway for the missing, though first responders efforts were hindered by the lava flow, officials said.
The volcano, about 40km south-west of the capital Guatemala City, has been spewing black smoke and ash into the sky.
After awakening on Sunday, and for the second time this year, the Volcan de Fuego (Volcano of Fire) has generated strong pyroclastic flows in the Barrancas de Cenizas, Mineral, Seca, Taniluya, Las Lajas and Barranca Honda localities, the National Coordinator for Disaster Reduction in Guatemala (Conred) said.
The road in front of Fuego volcano is seen covered with ash after the volcano erupted violently, in San Juan Alotenango, Guatemala June 3, 2018.
Guatemala's airport in the capital city has closed down while many villagers are being evacuated.
The Guatemalan government says around one million people have been affected by the eruption.
President Jimmy Morales said he had convened his ministers and was considering declaring a state of emergency in the departments of Chimaltenango, Escuintla and Sacatepequez.
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The volcano's peak soars 3,763 meters above sea level.
The eruption forced the Guatemala City's La Aurora worldwide airport to shut down its only runway.
"We have shut it down as a precautionary measure for the planes because the volcanic ash is harmful to the turbines", the airport spokesman, Francis Argueta said.
It is close to the popular tourist destination Antigua, which is known for its coffee plantations.
Workers and guests were evacuated from the La Reunion golf club. Locals, meanwhile, have shared dramatic photos and videos showing a massive ash column reaching to the sky. "That could cause more mud flows and nearby rivers to burst their banks", said Eddy Sanchez, director of Guatemala's seismological, volcanic and meteorological institute.
The head of the National Disaster Prevention Authority Sergio Cabañas told a local radio station that a river of lava had changed course towards a small town.
Disaster agency spokesman David de Leon says about 300 people have been evacuated from nearby villages, which are being blanketed by ash as fiery smoke billows almost four miles into the sky.
BBC News reports officials advised residents to wear masks as ash fell.