André Weil was born in Paris to agnostic Alsatian Jewish parents who fled the annexation of Alsace-Lorraine by the German Empire after the Franco-Prussian War in 1870–71. The famous Philosopher Simone Weil was Weil's only sibling. He studied in Paris, Rome and Göttingen and received his doctorate in 1928. While in Germany, Weil befriended Carl Ludwig Siegel. Starting in 1930, he spent two academic years at Aligarh Muslim University. Aside from mathematics, Weil held lifelong interests in classical Greek and Latin literature, in Hinduism and Sanskrit literature: he taught himself Sanskrit in 1920. After teaching for one year in Aix-Marseille University, he taught for six years in Strasbourg. He married Éveline in 1937.

Weil introduced the adele ring in the late 1930s, following Claude Chevalley's lead with the ideles, and gave a proof of the Riemann–Roch theorem with them (a version appeared in his Basic Number Theory in 1967). His 'matrix divisor' (vector bundle avant la lettre) Riemann–Roch theorem from 1938 was a very early anticipation of later ideas such as moduli spaces of bundles. The Weil conjecture on Tamagawa numbers proved resistant for many years. Eventually the adelic approach became basic in automorphic representation theory. He picked up another credited Weil conjecture, around 1967, which later under pressure from Serge Lang (resp. of Serre) became known as the Taniyama–Shimura conjecture (resp. Taniyama–Weil conjecture) based on a roughly formulated question of Taniyama at the 1955 Nikkō conference. His attitude towards conjectures was that one should not dignify a guess as a conjecture lightly, and in the Taniyama case, the evidence was only there after extensive computational work carried out from the late 1960s.

Other significant results were on Pontryagin duality and differential geometry. He introduced the concept of a uniform space in general topology, as a by-product of his collaboration with Nicolas Bourbaki (of which he was a Founding Father). His work on sheaf theory hardly appears in his published papers, but correspondence with Henri Cartan in the late 1940s, and reprinted in his collected papers, proved most influential.

In January 1941, Weil and his family sailed from Marseille to New York. He spent the remainder of the war in the United States, where he was supported by the Rockefeller Foundation and the Guggenheim Foundation. For two years, he taught undergraduate mathematics at Lehigh University, where he was unappreciated, overworked and poorly paid, although he didn't have to worry about being drafted, unlike his American students. But, he hated Lehigh very much for their heavy teaching workload and he swore that he would never talk about "Lehigh" any more. He quit the job at Lehigh, and then he moved to Brazil and taught at the Universidade de São Paulo from 1945 to 1947, where he worked with Oscar Zariski. He then returned to the United States and taught at the University of Chicago from 1947 to 1958, before moving to the Institute for Advanced Study, where he would spend the remainder of his career. He was a Plenary Speaker at the ICM in 1950 in Cambridge, Massachusetts, in 1954 in Amsterdam, and in 1978 in Helsinki. In 1979, Weil shared the second Wolf Prize in Mathematics with Jean Leray.

He also wrote several books on the history of Number Theory. Weil was elected Foreign Member of the Royal Society (ForMemRS) in 1966.

Weil made substantial contributions in a number of areas, the most important being his discovery of profound connections between algebraic geometry and number theory. This began in his doctoral work leading to the Mordell–Weil theorem (1928, and shortly applied in Siegel's theorem on integral points). Mordell's theorem had an ad hoc proof; Weil began the separation of the infinite descent argument into two types of structural approach, by means of height functions for sizing rational points, and by means of Galois cohomology, which would not be categorized as such for another two decades. Both aspects of Weil's work have steadily developed into substantial theories.