Army troops and police officers surrounded the Granja Penal Canada prison, which holds 3,100 inmates, following violence that erupted on Sunday.
After police went inside to round up prisoners and search for reported firearms, AFP saw groups of inmates made to stand or sit on the grounds as officers monitored them, batons in hand.
More than 2,000 police were deployed at the prison, backed by dozens of soldiers and an armored vehicle. The facility is circled by three security fences, one of them electrified.
The violence appeared to have been triggered during a prison yard football game, with tensions between general prisoners and bullying gang members spilling over, a police chief told AFP on condition of anonymity.
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The episode occurred during visiting hours, sending wives and girlfriends running, some with children.
"You could hear shooting all around, and I ran out with three of my children, which is why I had to go back to get the other one," one visitor, Heidy Solares, who came with four children told AFP. She didn't know what happened to her incarcerated husband, Estaban.
"There was no immediate action in order to avoid a confrontation between prisoners and police," he told reporters.
Guatemalan media overnight showed images of black body bags holding inmates who were shot or stabbed to death being taken from the prison to a morgue.
"We are coordinating with prosecutors on an investigation," Sosa said.
He added that the violence by the prisoners did not seem to be an attempt to escape.
Guatemala, El Salvador and Honduras are plagued by turf battles between violent street gangs fighting to control impoverished communities.