At least 29 people were killed in a quake-triggered landslide in the village of Planas in Guihulngan City, mayor Ernesto Reyes said.
Reyes said 10 others died due to a landslide on the Guihulngan national road.
A nine-year-old girl was killed when a wall collapsed in nearby Tayasan township while 12 other fatalities were listed by the Provincial Disaster Risk Reduction and Management Council.
Roel Degamo, governor of Negros Oriental, said the earthquake had damaged eight bridges, three of which were no longer passable.
Degamo said soldiers and police are now conducting rescue and relief operations. The governor also suspended all classes and work in government offices for the rest of the day.
By Tuesday morning, residents of Negros Oriental province were allowed to return to their homes. Degamo ordered the local rescue organ to prepare relief goods for local residents.
The Philippines sits in the so-called Pacific Ring of Fire with frequent earthquakes and volcanic activities.
The deadliest earthquake in the country happened on August 16, 1976 when an ensuing tsunami killed between 5,000 and 8,000 people in the Moro Gulf region in southern Philippines.