Molina studied chemical engineering at the National Autonomous University of Mexico (B.S., 1965) in Mexico City and received an advanced degree from the University of Freiburg (1967) in West Germany before returning to his alma mater to become an associate professor (1967–68). He resumed his education in the United States at the University of California, Berkeley (Ph.D., 1972), where he worked for a year before joining Rowland at the University of California, Irvine. The pair conducted experiments on pollutants in the atmosphere, discovering that CFC gases rise into the stratosphere, where ultraviolet radiation breaks them into their component elements of chlorine, fluorine, and carbon. There, each chlorine atom is capable of destroying about 100,000 ozone molecules before becoming inactive.

Molina was the principal author of the paper describing their theories, which was published in the scientific journal Nature in 1974. Their findings sparked a nationwide debate on the environmental effects of CFC gases and were validated in the mid-1980s when a region of stratospheric ozone depletion, known as the ozone hole, was discovered over Antarctica. Molina worked in the Jet Propulsion Laboratory at the California Institute of Technology in Pasadena from 1982 to 1989, when he became a professor at the Massachusetts Institute of Technology in Cambridge.