After graduation in chemistry he worked for a year at the Philip R. Park Research Foundation taking care of an animal colony and assisting with growth experiments on synthetic amino acid diets.

In 1963, he was sole author of a classic paper in the Journal of the American Chemical Society in which he reported a method he called "solid phase peptide synthesis".

[5][6][7][8][9][10][11] Dr. Merrifield's method greatly stimulated progress in biochemistry, pharmacology and medicine, making possible the systematic exploration of the structural basis of the activities of enzymes, hormones and antibodies.

In 1993, Jeffrey I. Seeman published Life during a Golden Age of Peptide Chemistry, Merrifield's autobiography, in the series "Profiles, Pathways, and Dreams" for the American Chemical Society.

After raising their 6 children, James, Nancy, Betsy, Cathy, Laurie and Sally, his wife Elizabeth (Libby), a biologist by training, joined the Merrifield laboratory at Rockefeller University where she worked for over 23 years.