Having graduated from the Agricultural Institute in his native city of Moscow, Vavilov continued his studies firstly in England under William Bateson and then in France at the Vilmoren Institution. Back in Russia he was appointed, in 1917, both professor of genetics and selection at the Agricultural Institute, Voronezh, and professor of agriculture at Saratov University. Three years later he took over the directorship of the Bureau of Applied Botany, Petrograd (now St. Petersburg), which later became the All Union Institute of Plant Industry. The institute flourished under Vavilov's leadership, becoming the center for over 400 research institutes throughout the Soviet Union. In 1929 he became the first president of the Academy of Agricultural Sciences.

During the years 1916–1933 Vavilov led several plant-collecting expeditions to countries all around the globe. The purpose was to gather material of potential use in crop-breeding programs, particularly the wild relatives and ancestors of cultivated plants. He was highly successful in this, his collection numbering some 250,000 accessions by 1940. This was the first large-scale attempt to conserve and utilize the immensely valuable genetic resources upon which crop improvement relies.

A second important consequence of these travels was Vavilov's observation that the genetic diversity of crop relatives is concentrated in certain areas that he termed ‘gene centers’, postulating that these correspond to regions where agriculture originated. The theory and the exact number of centers have since been modified but the recognition of such areas is an invaluable aid to other plant hunters. He also found certain regularities between unrelated genera in such centers, described in The Law of Homologous Series in Variation (1922).

Vavilov's excellent work was gradually stifled by the intrusion of politics into Soviet biology in the 1930s. His belief in the advances in genetics made by Mendel and T. H. Morgan brought him into conflict with the government-backed Trofim Lysenko, who was returning to a Lamarckian view of inheritance. The 1937 International Congress of Genetics, due to be held in Moscow in view of the strides made in Soviet genetics under Vavilov, was canceled by the Lysenkoists. Vavilov was arrested in 1940 while plant collecting and died three years later in a Siberian labor camp.

Today Vavilov is recognized in his own country as an outstanding scientist, the Vavilov Institute being named in his honor.