Picard became a lecturer at the University of Paris (Paris I–XIII, Universities of) in 1878 and a professor at the University of Toulouse the following year. From 1881 to 1898 he held various posts with the University of Toulouse and the École Normale Supérieure (now part of the Universities of Paris), and in 1898 he was appointed a professor at the University of Paris. In 1917 he was elected permanent secretary for the mathematical sciences in the French Academy of Sciences (Sciences, Academy of). After World War I he led a decade-long movement to boycott German scientists and mathematicians.

Picard made his name in 1879 when he proved that an entire function (a function that is defined and differentiable for all complex numbers (complex number)) takes every finite value, with one possible exception. Then, inspired by Niels Henrik Abel (Abel, Niels Henrik) of Norway and Bernhard Riemann (Riemann, Bernhard) of Germany, he generalized Riemann's work to complex functions of two variables. His study of the integrals attached to algebraic surfaces and the related topological questions developed into an important part of algebraic geometry, with varied applications to topology and functional analysis (analysis).

Picard also worked on Fuchsian and Abelian functions and on the allied theories of discontinuous and continuous groups of transformation. His research was expounded in a treatise that he published with Georges Simart, Théorie des fonctions algébriques de deux variables indépendantes, 2 vol. (1897, 1906; “Theory of Algebraic Functions of Two Independent Variables”).

Picard successfully revived the method of successive approximations to prove the existence of solutions to differential equations (differential equation). He also created a theory of linear differential equations, analogous to the Galois theory of algebraic equations. His studies of harmonic vibrations, coupled with the contributions of Hermann Schwarz of Germany and Henri Poincaré (Poincaré, Henri) of France, marked the beginning of the theory of integral equations (integral equation).