The one-week war games dubbed "Vostok-2018" (East-2018) "have begun" in far eastern Russia and the Pacific Ocean, the Defense Ministry said in a statement.
He released video footage of military vehicles, planes, helicopters and ships that were put in position for the initial stage of the simulations.
The exercises, which include the armies of China and Mongolia, have been condemned by NATO as a trial of "large-scale conflict".
President Vladimir Putin is expected to attend Vostok-2018 after organizing an economic forum in the Russian city of Vladivostok, in the Russian Far East, where his Chinese counterpart, Xi Jinping, is one of the most important guests.
The military exercises take place at a time of growing tension between Moscow and the West due to accusations of Russian interference in Western affairs and ongoing conflicts in Ukraine and Syria.
The Russian army has compared the demonstration of strength with the war games of the USSR in 1981 that saw between 100,000 and 150,000 Warsaw Pact soldiers take part in "Zapad-81" (West-81) – the largest military exercises in the Soviet era.
But Defense Minister Sergei Shoigu said these exercises are even bigger, with 300,000 soldiers, 36,000 military vehicles, 1,000 aircraft and 80 warships participating in the drills.
"Imagine 36,000 military vehicles moving at the same time: tanks, armored personnel carriers, infantry fighting vehicles, and all of this, of course, in conditions as close as possible to a combat situation," said Shoigu.
The Russian army is deploying all its latest additions to the event: Iskander missiles that can carry nuclear warheads, T-80 and T-90 tanks and their recent Su-34 and Su-35 fighters.
At sea, the Russian fleet is deploying several frigates equipped with Kalibr missiles that have been used in Syria.
On Wednesday there will be games with anti-aircraft technology, while the main event will be on Thursday, the Ministry of Defense told journalists covering the event in eastern Siberia.
NATO said that Vostok-2018 "demonstrates Russia's approach to the exercise of the conflict on a large scale."
"It fits into a pattern that we have seen for a while: a more assertive Russia, which significantly increases its defense budget and military presence," said alliance spokesman Dylan White in late August.
Last month, Kremlin spokesman Dmitry Peskov said that Russia's "ability to defend itself in the current international situation, which is often aggressive and unfriendly to our country, is justified, essential and has no alternative."
Relations between Russia and the West declined sharply in 2014 with the annexation of Crimea by Moscow and the subsequent conflict in eastern Ukraine.
The Kremlin also accused NATO of expanding to the west and threatening Russian national security.
Moscow has increased the number of its large-scale military exercises in the Caucasus, the Baltic and the Arctic in recent years.
Russia's previous military exercise in the region, Vostok-2014, was almost half the size, with 155,000 soldiers participating.
The country's war games in Eastern Europe last year, Zapad-2017, saw 12,700 soldiers participate according to Moscow. Ukraine and the Baltic countries said that the real number was much higher.