The air strike was launched after the Russian forces in Syria received intelligence that a meeting of ISIS leaders was being planned, the ministry said in a statement posted on its Facebook page.
"On May 28, after drones were used to confirm the information on the place and time of the meeting of ISIS leaders, between 00:35 and 00:45, Russian air forces launched a strike on the command point where the leaders were located," the statement said.
"According to the information which is now being checked via various channels, also present at the meeting was ISIS leader Abu Bakr al-Baghdadi, who was eliminated as a result of the strike," the ministry said.
The U.S.-led coalition fighting ISIS said it could not confirm the Russian report that Baghdadi may have been killed.
The strike is believed to have killed several other senior leaders of the group, as well as around 30 field commanders and up to 300 of their personal guards, the Russian defence ministry statement said.
The ISIS leaders had gathered at the command centre, in a southern suburb of Raqqa, to discuss possible routes for the militants' retreat from the city, the statement said.
The United States was informed in advance about the place and time of the strike, the Russian military said.
Russian forces support the Syrian government which is fighting against ISIS mainly from the west, while a U.S.-led coalition supports Iraqi government forces fighting against ISIS from the east.
The last public video footage of Baghdadi shows him dressed in black clerical robes declaring his caliphate from the pulpit of Mosul's medieval Grand al-Nuri mosque back in 2014.
Born Ibrahim al-Samarrai, Baghdadi is a 46-year-old Iraqi who broke away from al Qaeda in 2013, two years after the capture and killing of the group's leader Osama bin Laden.
Rami Abdulrahman, director of the Syrian Observatory for Human Rights, cast doubt on the report Baghdadi may have been killed. He said that according to his information, Baghdadi was located in another part of Syria at the end of May.
"The information is that as of the end of last month Baghdadi was in Deir al-Zor, in the area between Deir al-Zor and Iraq, in Syrian territory," he said by phone.
Questioning what Baghdadi would have been doing in that location, he said: "Is it reasonable that Baghdadi would put himself between a rock and a hard place of the (U.S.-led) coalition and Russia?"