Zariski was born Oscher (also transliterated as Ascher or Osher) Zaritsky to a Jewish family (his parents were Bezalel Zaritsky and Hanna Tennenbaum) and in 1918 studied at the University of Kiev. He left Kiev in 1920 to study at the University of Rome where he became a disciple of the Italian school of algebraic geometry, studying with Guido Castelnuovo, Federigo Enriques and Francesco Severi.

Zariski wrote a doctoral dissertation in 1924 on a topic in Galois theory, which was proposed to him by Castelnuovo. At the time of his dissertation publication, he changed his name to Oscar Zariski.

Zariski emigrated to the United States in 1927 supported by Solomon Lefschetz. He had a position at Johns Hopkins University where he became professor in 1937. During this period, he wrote Algebraic Surfaces as a summation of the work of the Italian school. The book was published in 1935 and reissued 36 years later, with detailed notes by Zariski’s students that illustrated how the field of algebraic geometry had changed. It is still an important reference.

After spending a year 1946–1947 at the University of Illinois at Urbana–Champaign, Zariski became professor at Harvard University in 1947 where he remained until his retirement in 1969. In 1945, he fruitfully discussed foundational matters for algebraic geometry with André Weil. Weil’s interest was in putting an abstract variety theory in place, to support the use of the Jacobian variety in his proof of the Riemann hypothesis for curves over finite fields, a direction rather oblique to Zariski’s interests. The two sets of foundations weren’t reconciled at that point.

Zariski proposed the first example of a Zariski surface in 1958.

Zariski was awarded the Steele Prize in 1981, and in the same year the Wolf Prize in Mathematics with Lars Ahlfors. He wrote also Commutative Algebra in two volumes, with Pierre Samuel. His papers have been published by MIT Press, in four volumes. In 1997 a conference was held in his honor in Obergurgl, Austria.