Pople was born in Burnham-on-Sea, Somerset, and gained his PhD in mathematics in 1951 at Cambridge. In 1964 he became professor of chemical physics at Carnego-Mellon University, Pittsburgh, and in 1986 moved to Northwestern University as professor of chemistry. In 1998 he shared the Nobel Prize for chemistry with Walter Kohn. Pople received his award for the development of computational methods in quantum chemistry.

Pople developed the whole quantum-chemical methodology currently used in various areas of chemistry. This makes it possible to study the configurations and properties of molecules and how they interact, using the basic principles of quantum mechanics. Details of a molecule or a reaction are fed to a computer, which outputs a list of properties of the molecule or describes how the reaction will proceed. Pople's main contribution to the process was the development in 1970 of a user-friendly program known as GAUSSIAN-70, now used by theoretical research chemists throughout the world. He continued to refine the methodology, accumulating a well-documented model chemistry, which by the early 1990s was able to incorporate Kohn's density-function theory.