Regional Governor Vyacheslav Gladkov said the blast had left a huge crater about 20 metres (60 ft) wide in the city centre.
Three people were injured and several buildings were damaged, he said. One apartment block was evacuated.
A Su-34 fighter-bomber jet accidentally released the bomb, the ministry said.
The defence ministry said the bomb fell at 22:15 local time (19:15 GMT) on Thursday. There was no explanation for the bombing other than what it described as an “abnormal descent of aviation ammunition”.
The bomb landed at an intersection of two roads not far from the city centre and next to residential buildings.
Two women were taken to hospital for treatment and a nine-storey apartment block was evacuated because of potential structural damage, Mr Gladkov said.
An investigation is under way.
Photos and videos on social media show apartments damaged by the blast, and one car ended up on the roof of a local shop next door to a block of flats.
The regional governor said Belgorod’s residents had endured a difficult night but would get through it.
Belgorod – a city of 370,000 – is around 25 miles (40 km) from the Ukrainian border. It lies just north of Ukraine’s second city, Kharkiv, and people there have been living in fear of Ukrainian shelling since the Russian invasion of Ukraine last year.
Russian jets also regularly fly over the city on their way to Ukraine.
