Zaytsev was born in Yeleninskoye, Orenburg Governorate in a peasant family of Russian ethnicity and grew up in the Ural Mountains, where he learned marksmanship by hunting deer and wolves with his grandfather and older brother.
He graduated from seven classes of junior high school. In 1930 he graduated from a construction college in the city of Magnitogorsk, where he received the specialty of a fitter. He graduated from accounting courses.
He was assigned to the 1047th Rifle Regiment of the 284th "Tomsk" Rifle Division, which became part of the 62nd Army at Stalingrad on 17 September 1942.
On 22 February 1943, Zaytsev was awarded the title Hero of the Soviet Union. He returned to the front and finished the war at the Battle of the Seelow Heights in Germany, with the military rank of captain. He became a member of the Communist Party in 1943.
Zaytsev settled in Kiev, where he studied at a textile university before obtaining employment as an engineer. He rose to become the director of a textile factory in Kiev and remained in that city until he died on 15 December 1991 at the age of 76, eleven days before the dissolution of the Soviet Union.
A feature-length film, Enemy at the Gates (2001), starring Jude Law as Zaytsev, was based on part of William Craig's book Enemy at the Gates: The Battle for Stalingrad (1973), which includes a "snipers' duel" between Zaytsev and a Wehrmacht sniper school director, Major Erwin König. Zaytsev indicates in his own memoirs that a three-day duel did occur and that the sniper he killed was the head of a sniper school near Berlin.
On 31 January 2006, Vasily Zaytsev was reburied on Mamayev Hill in Volgograd with full military honors.