The bodies of the 30-year-old mother and her children — aged six, nine and 12 — were found with bullet wounds in a home in a popular neighborhood south of the capital, fire department spokesman Edwin Villagran said.
Local media said the attack was tied to a turf dispute, but authorities did not reveal more details about the investigation.
Guatemala is experiencing a wave of violence that claims an average of 16 lives daily, one of the highest rates in Latin America.
Authorities estimate about half of all violent deaths are associated with disputes over territory between various gangs and drug-trafficking groups.