Ingram, born Immerwahr in Breslau (now Wrocław in Poland), was brought to Britain as a refugee from Nazi Germany as a child. He was educated at Birkbeck College, London, where he obtained his PhD in 1949. After working briefly at Rockefeller and Yale he returned to England and joined the staff of the Medical Research Council's molecular biology unit at the Cavendish Laboratory, Cambridge, in 1952. In 1958 however he moved to the Massachusetts Institute of Technology where he has served as professor of biochemistry since 1961 and as John and Dorothy Wilson Professor of Biology since 1988.

By the mid 1950s it was clear to Francis Crick that it should be possible, and was indeed essential, for molecular biology to be able to show that mutant genes produced changes in the amino acid sequences of proteins. Although such a claim was central to the supposed revolution in molecular biology, there was, as Crick realized in 1955, no direct evidence that proteins are in fact coded by genes.

Consequently Crick and Ingram attempted to reveal such a change in the lysozyme of fowl eggs. However, although they succeeded in distinguishing differences between lysozymes from such different birds as duck and pheasant, they failed to find any difference in lysozymes between two hens of the same species. At this point however Max Perutz gave Ingram some sickle-cell hemoglobin (hemoglobin S) to work with. (Hemoglobin S, possessed by sufferers of a crippling anemia, had been distinguished from normal hemoglobin A by Linus Pauling and his student Harvey Itano in 1949.) Ingram split the hemoglobin into smaller units by using the enzyme trypsin to break the peptide bonds. He then separated these units by electrophoresis and paper chromatography. This allowed him to show that hemoglobin S differs from normal hemoglobin at just one site where the amino acid valine replaces the glutamic acid of the A form. Although it came as a surprise that the alteration of one amino acid in over 500 could produce such major effects, it also dramatically established that molecular biology was not just an abstract and remote branch of structural chemistry.

Ingram went on to show that this and other point mutations of hemoglobin could be used to trace the evolutionary history of vertebrates, work reported in his The Hemoglobins in Genetics and Evolution (1963).