Fraenkel-Conrat, son of the noted gynecologist Ludwig Fraenkel, was born in Breslau (which was then in Germany and is now Wrocław in Poland). He left Germany for Britain after graduating MD from the University of Breslau in 1934. Having gained his PhD for work on ergot alkaloids and thiamine from the University of Edinburgh in 1936, he moved on to America, where he settled and became an American citizen in 1941. He joined the faculty of the University of California at Berkeley in 1951, becoming professor of virology in 1955 and professor emeritus in 1981.

Fraenkel-Conrat, working with the tobacco mosaic virus (TMV), an RNA virus, provided evidence that RNA, like DNA, can act as the genetic material. This he did by separating the RNA and protein portions of the virus, and then reassembling them to make a fully infective virus. Moreover Fraenkel-Conrat demonstrated that, while the isolated protein was quite dead, the isolated RNA showed slight signs of infectivity. This work was reported in a paper by Fraenkel-Conrat and Robley C. Williams Reconstitution of Tobacco Mosaic Virus from Its Inactive Protein and Nucleic Acid Components (1955). In later work with Wendell Stanley the complete amino-acid sequence, consisting of 158 amino acids, of the TMV protein was established.

Fraenkel-Conrat, in collaboration with R. R. Wagner, edited one of the basic texts of modern virology, Comprehensive Virology (19 vols.; 1974–84).