Authorities say more than 4,000 houses were reported damaged by the 5.3 magnitude temblor, which struck at 1:56 a.m. local time about 75 miles south of the capital, Belgrade.
People ran from their homes across the country as the quake rocked a wide area.
The city of Kraljevo sustained the most damage and was cast into darkness after the quake knocked out power across central Serbia.
Officials say schools and hospitals sustained significant damage. Many shop windows across Kraljevo were broken, while some cars were smashed when concrete blocks fell on them.
In the village of Vitanovac, located very near the epicenter, about 70 percent of houses were severely damaged, many with their roofs collapsed.
Several strong aftershocks jolted the region as rescue efforts were under way.