After World War II, the rapid growth of nuclear physics and chemistry meant that research needed more and more powerful accelerators, which required large areas.

The rapid increase of students led to the independence of the Orsay Campus on 1 March 1965 (sometimes called "Faculté des sciences d'Orsay" thereafter).

Paris-Sud hosted a great number of laboratories on its large (236 ha) campus.

Pierre-Gilles de Gennes and Albert Fert, two Nobel Prize winners of physics, were affiliated to the University of Paris-Sud.

Among them are the Fields medalists Pierre Deligne, Laurent Lafforgue, Jean-Christophe Yoccoz, Wendelin Werner and Ngô Bảo Châu.