Lt Gen Igor Kirillov, the head of the military's chemical, biological and radiological weapons unit, was killed with his assistant when the blast went off as they left a building in a residential area in south-east Moscow.
A source in Ukraine's SBU security service said that Kyiv was behind the attack.
Kirillov, who was placed under sanctions by Britain in October over the alleged use of chemical weapons in Ukraine, is the most senior Russian military official killed in an assassination away from the frontlines since the start of the Kremlin's offensive in Ukraine nearly three years ago.
Speaking at a meeting with senior Russian leadership, Dmitry Medvedev, the deputy head of the country's security council, said Moscow would avenge the killing. "We must do everything to eliminate those who ordered the assassination of Gen Kirillov, namely the military-political leadership of Ukraine," he said.
Russia's investigative committee said Kirillov was killed after "an explosive device planted in a scooter parked near the entrance of a residential building was activated".
Footage circulating online, seemingly captured by the dashcam of a car, showed two men leaving the apartment just before an explosion that killed them both.
Mash, a Telegram channel with ties to Russian law enforcement, published a photograph of two bodies lying in the snow surrounded by shards of glass from broken windows outside an apartment building.
Ukraine's SBU had a day earlier put out an arrest warrant for Kirillov for alleged war crimes against Kyiv's forces.
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