Edwin Krebs is not to be confused with Hans Adolf Krebs (1900–1981), who was also a Nobel Prize–winning biochemist and who discovered the citric acid cycle, which is also known as the Krebs cycle.

Krebs was born in Lansing, Iowa, the third child of william Carl Krebs, a Presbyterian minister and Louise Helen (Stegeman) Krebs. The family moved frequently due to the nature of his father's work, though they settled in Greenville, Illinois when Krebs was six and remained there until his father's unexpected death in 1933. Louise Krebs decided to move her family to Urbana, Illinois, where Krebs's elder brothers were attending the University of Illinois at Urbana-Champaign. Krebs attended Urbana High School, and enrolled at the University of Illinois at Urbana-Champaign in 1936. In his fourth year of study Krebs had decided to either pursue a higher degree in organic chemistry or study Medicine. Receiving a scholarship to attend Washington University School of Medicine in St. Louis, he chose the latter.

The School of Medicine afforded Krebs the opportunity to train as a physician as well as to gain experience in medical research. Following graduation in 1943, he undertook an 18-month residency at Barnes Hospital in St. Louis and then went on active duty as a medical officer in the Navy. Krebs was discharged from the Navy in 1946 and was unable to immediately return to hospital work; he was advised to study basic science instead. He chose to study biochemistry and was postdoctoral fellow to Carl and Gerty Cori, working on the interaction of protamine with rabbit muscle phosphorylase. At the completion of his two years' study, Krebs decided to continue his career as a biochemist.

In 1948 Krebs accepted a position as assistant professor of biochemistry at the University of Washington, Seattle. When Edmond H. Fischer arrived at the Department in 1953, the pair decided to work on the enzymology of phosphorylase. During the course of their study they were able to observe the mechanism by which interconversion of the two forms of phosphorylase takes place: reversible protein phosphorylation.

Krebs's interest in teaching and administration led him to leave the University of Washington to become the founding chairman of the Department of Biochemistry at the University of California, Davis. In 1977 he returned to the University of Washington as Chairman of the Department of Pharmacology.

Explained simply, in reversible protein phosphorylation a protein kinase takes a phosphate group from adenosine triphosphate (ATP) and attaches it to a specific site on a protein, introducing both extra mass and negative charge at that site. This can alter the protein's shape and turn its function in a biological process up or down, either by changing its activity or its ability to bind to another protein. The protein can be converted back to its original state by a protein phosphatase that removes the phosphate. This cycle controls numerous metabolic processes, and plays a central role in the regulation of cell division, shape, and motility. Derangement of specific protein phosphorylation pathways is important in human disease, including cancer and diabetes. Fischer and Krebs were awarded the Nobel Prize for Physiology or Medicine in 1992 for the discovery of reversible protein phosphorylation, .

Krebs died on December 21, 2009. He is survived by his wife Virginia and three children.