He was the son of a Russian Jewish immigrant couple,[5] Sarah Brodsky, a homemaker, and Harry Berg, a clothing manufacturer.

[8] After completing his graduate studies, Berg spent two years (1952–1954) as a postdoctoral fellow with the American Cancer Society, working at the Institute of Cytophysiology in Copenhagen, Denmark, and the Washington University School of Medicine, and spent additional time in 1954 as a scholar in cancer research with the department of microbiology at the Washington University School of Medicine.

After 1959, Berg moved to Stanford University, where he taught biochemistry from 1959 until 2000 and served as director of the Beckman Center for Molecular and Genetic Medicine from 1985 until 2000.

This resulted in the understanding of how foodstuffs are converted to cellular materials, through the use of isotopic carbons or heavy nitrogen atoms.

Paul Berg's doctorate paper is now known as the conversion of formic acid, formaldehyde and methanol to fully reduced states of methyl groups in methionine.

Berg is arguably most famous for his pioneering work involving gene splicing of recombinant DNA.

The previous year, Berg and other scientists had called for a voluntary moratorium on certain recombinant DNA research until they could evaluate the risks.

Berg was awarded one-half of the 1980 Nobel Prize in Chemistry, with the other half being shared by Walter Gilbert and Frederick Sanger.