In his professional work, he focused on molecular configuration, and described results of over ten years of research in a publication on properties of chemical bonds and the structure of molecules and crystals. In recognition for expanding the knowledge in this field and for applying it to the study of complex substances, he was awarded the Nobel Prize in chemistry in 1954.

At the end of World War II, he developed an interest in potentially dangerous effects of nuclear fallout and the influence of radiation on the structure of molecules in the human body as well as in the forces behind the nuclear explosion and its thermal effect. He calculated the probability of the incidence of foetal deformities in subsequent generations as a consequence of exposition to radiation due to nuclear testing. He opposed development of the hydrogen bomb and advocated a ban on nuclear testing as the first step towards disarmament. In 1958, he presented the United Nations with the petition signed by 9,235 scientists calling for an end to nuclear-weapon testing. In his book “No More War”, he put forward his arguments not only against further use and testing of nuclear weapons, but also against war itself. He proposed establishing a World Peace Research Organization which would deal with “the problem of keeping peace”.

In the years 1927–64, he worked at his Alma mater (Caltech), where he also served as a dean of the Chemistry and Chemical Engineering Division for 22 years, gaining the opinion of an excellent teacher. He was awarded honorary doctorates by universities of seven different countries. He is the only Nobel Prize winner in history who has won two undivided Nobel Prizes.

The first Limited Nuclear Test Ban Treaty was signed in July 1963. It entered into force on 10 October, the day when it was announced that Linus Pauling was awarded the Nobel Peace Prize that had been held over from 1962.