At least 48 people died in the temblor, President Otto Perez Molina said in a Twitter post Wednesday night, and doctors treated at least 150 others for injuries.
Earlier Wednesday, Guatemala's disaster relief agency said 29 people were missing and hundreds had lost their homes.
Residents felt the 7.4-magnitude quake throughout Central America and as far north as Mexico City. Its epicenter was about 15 miles off the western coastal town of Champerico, at a depth of 26 miles.
It was the strongest quake to hit Guatemala since 1976, the president told reporters, when a 7.5-magnitude quake killed 23,000 people.
"Fortunately, the damage that we have is not at the same level," Perez Molina said Wednesday.
Roads collapsed in multiple locations around the Pacific coastal region of Guatemala, Perez Molina said.
Photos on the Facebook page of the nation's disaster relief agency showed rubble crushing cars and damage to the ceiling at a school in the department of San Marcos.
There were reports of homes and schools destroyed in western Guatemala, Perez Molina told CNN en Español. Many people fled buildings when the tremor first hit.
Some 60,000 people remained without power in the country because of the quake, the state-run AGN news agency reported.
It was fortunate that the school year in Guatemala had recently come to end, so that no children were inside the school buildings that were damaged, Perez Molina said.
In Guatemala City, 140 miles away from the quake's epicenter, the quake made the desk and printer sway side to side in Fernando McDonald's home office.
Fearing powerful aftershocks, the government issued a "red alert" that warns people to take precautions, such as evacuating tall buildings. The alert stretches along the country's entire Pacific coast.