After graduating in 1947, Arkhipov served in the submarine Service aboard boats in the Black Sea, Northern and Baltic Fleets.

In July 1961, Arkhipov was appointed deputy commander and therefore executive officer of the new Hotel-class ballistic missile submarine K-19. After a few days of conducting exercises off the south-east coast of Greenland, the submarine developed an extreme leak in its reactor coolant system. This leak led to failure of the cooling system. Radio communications were also affected, and the crew was unable to make contact with Moscow. With no backup systems, Commander Zateyev ordered the seven members of the Engineer crew to come up with a solution to avoid nuclear meltdown. This required the men to work in high radiation levels for extended periods. They eventually came up with a secondary coolant system and were able to keep the reactor from a meltdown. Although they were able to save themselves from a nuclear meltdown, the entire crew, including Arkhipov, were irradiated. All members of the Engineer crew and their divisional officer died within a month due to the high levels of radiation they were exposed to. Over the course of two years, fifteen more sailors died from the after-effects.

On 27 October 1962, during the Cuban Missile Crisis, a group of eleven United States Navy destroyers and the aircraft carrier USS Randolph located the diesel-powered, nuclear-armed Soviet Foxtrot-class submarine B-59 near Cuba. Despite being in international waters, the Americans started dropping signaling depth charges, explosives intended to force the submarine to come to the surface for identification. There had been no contact from Moscow for a number of days and, although the submarine's crew had earlier been picking up U.S. civilian radio broadcasts, once B-59 began attempting to hide from its U.S. Navy pursuers, it was too deep to monitor any radio traffic. Those on board did not know whether war had broken out or not. The captain of the submarine, Valentin Grigorievitch Savitsky, decided that a war might already have started and wanted to launch a nuclear torpedo.

Arkhipov continued in Soviet Navy Service, commanding submarines and later submarine squadrons. He was promoted to rear admiral in 1975, and became head of the Kirov Naval Academy. Arkhipov was promoted to vice admiral in 1981 and retired in the mid 1980s.

Vasili Arkhipov was married to Olga Arkhipova. They remained together up until his death in 1998. They had a daughter named Yelena.

The K-19 accident was the basis for the 2002 film, K-19: The Widowmaker.

Arkhipov was born into a peasant family in the town of Staraya Kupavna, near Moscow. He was educated in the Pacific Higher Naval School and participated in the Soviet–Japanese War in August 1945, serving aboard a minesweeper. He transferred to the Caspian Higher Naval School and graduated in 1947.

In recognition of his actions onboard B-59, Arkhipov received the first "Future of Life Award," which was presented posthumously to his family in 2017. Offered by the Future of Life Institute, this award recognizes exceptional measures, often performed despite personal risk and without obvious reward, to safeguard the collective Future of humanity.