Ester Molina, Mario's aunt, and an already established chemist, nurtured his interests and aided him in completing more complex chemistry experiments.

[12] At this time, Mario knew he wanted to pursue a career in chemistry, and at the age of 11, he was sent to a boarding school in Switzerland at Institut auf dem Rosenberg, where he learnt to speak German.

[13] At first Mario was disappointed when he arrived at the boarding school in Switzerland due to the fact that most of his classmates did not have the same interest in science as he did.

Between 1974 and 2004, Molina variously held research and teaching posts at University of California, Irvine, the Jet Propulsion Laboratory at Caltech, and the Massachusetts Institute of Technology (MIT), where he held a joint appointment in the Department of Earth Atmospheric and Planetary Sciences and the Department of Chemistry.

[5] On 1 July 2004, Molina joined the Department of Chemistry and Biochemistry at University of California, San Diego, and the Center for Atmospheric Sciences at the Scripps Institution of Oceanography.

[21] He served as a co-chair of the Vatican workshop and co-author of the report Well Under 2 Degrees Celsius: Fast Action Policies to Protect People and the Planet from Extreme Climate Change (2017) with Veerabhadran Ramanathan and Durwood Zaelke.

The report proposed 12 scalable and practical solutions which are part of a three-lever cooling strategy to mitigate climate change.

[32][33] This study soon led to research into chlorofluorocarbons (CFCs), apparently harmless gases that were used in refrigerants, aerosol sprays, and the making of plastic foams.

A thin layer of ozone floating high in the stratosphere protects lower levels of the atmosphere from that type of radiation.

[34][35] Molina and Rowland predicted that chlorine atoms, produced by this decomposition of CFCs, would act as an ongoing catalyst for the destruction of ozone.

When they calculated the amounts involved, they realized that CFCs could start a seriously damaging chain reaction to the ozone layer in the stratosphere.

[36][32][33] In 1974, as a postdoctoral researcher at University of California, Irvine, Molina and F. Sherwood Rowland co-authored a paper in the journal Nature highlighting the threat of CFCs to the ozone layer in the stratosphere.

Molina and Rowland followed up the short Nature paper with a 150-page report for the United States Atomic Energy Commission (AEC), which they made available at the September 1974 meeting of the American Chemical Society in Atlantic City.

This report and an ACS-organized press conference, in which they called for a complete ban on further releases of CFCs into the atmosphere, brought national attention.

Rowland and Molina's work was further supported by evidence of the long-term decrease in stratospheric ozone over Antarctica, published by Joseph C. Farman and his co-authors in Nature in 1985.

Ongoing work led to the adoption of the Montreal Protocol (an agreement to cut CFC production and use) by 56 countries in 1987, and to further steps towards the worldwide elimination of CFCs from aerosol cans and refrigerators.

By establishing this protocol, the amount of CFCs being emitted into the atmosphere decreased significantly, and while doing so, it has paced the rate of ozone depletion and even slowed climate change.

[12] Molina received numerous awards and honors,[5][6] including sharing the 1995 Nobel Prize in chemistry with Paul J. Crutzen and F. Sherwood Rowland for their discovery of the role of CFCs in ozone depletion.

[46] Molina won the 1987 Esselen Award of the Northeast section of the American Chemical Society, the 1988 Newcomb Cleveland Prize from the American Association for the Advancement of Science, the 1989 NASA Medal for Exceptional Scientific Advancement and the 1989 United Nations Environmental Programme Global 500 Award.

In 1990, The Pew Charitable Trusts Scholars Program in Conservation and the Environment honored him as one of ten environmental scientists and awarded him a $150,000 grant.

[56] On 19 March 2023, Molina was the subject of a Google Doodle in Mexico, the United States, Brazil, India, Germany, France, and other countries.