Carlos Perez, a spokesman for the national firefighters company, said the death toll is likely to rise, given the serious condition of the injured.
"Many of them had broken bones or severe head injuries. It's likely that many of them will die," Perez said.
The wreck occurred near the city of Cuilapa, about 50 miles east of Guatemala City.
The injured were taken to nearby hospitals for treatment. The dead included four children, four women and 37 men.
Guatemalan buses are frequently overloaded and must navigate rudimentary roads.