"At the site of the crash of the Sukhoi Su-34 in the courtyard of one of the residential area, the aircraft's fuel caught fire," the ministry said, shortly after images on social media showed buildings engulfed by flames.
Unconfirmed footage on social media showed a large fireball erupting from what appeared to be a multi-storey building. Agencies said the pilots had ejected and officials were trying to establish information about casualties on the ground.
A Su-34 bomber came down after one of its engines caught fire during takeoff, the Russian Defence Ministry said.
It said that both crew members bailed out safely, but the plane crashed into a residential area, causing a fire as tons of fuel exploded on impact.
The Kremlin said that President Vladimir Putin was immediately informed about the crash, and he ordered ministers of health and emergencies along with the local governor to head to the site.
Regional Gov. Veniamin Kondratyev said that emergency services were working to put out the fire.
Local authorities said that the massive blaze engulfed several floors of a nine-story apartment building and at least 17 apartments were affected. There was no immediate information about casualties.
The Defense Ministry said the plane that crashed had taken off for a training mission.
Russia launched a criminal investigation on Monday into the crash of a Su-34 fighter jet in the southern city of Yeysk, the country's investigative committee said.
"Military investigators are establishing the circumstances and causes of the incident," it said.
The Su-34 is a supersonic twin-engine bomber equipped with sophisticated sensors and weapons that has been a key strike component of the Russian air force. The aircraft has seen wide use during the war in Syria and the fighting in Ukraine.
