On 6 December 1919, it was recorded unanimously by the Board of the Faculty of Medicine of the University that there was an 'urgent need' to establish a Chair of Biochemistry in Oxford (Memorandum by the Board of the Faculty of Medicine, 22 Jan 1920, in OUA/HC/1/1/115, pp 47-8). In a letter to the Hebdomadal Council, the Board urged that 'as soon as opportunity [arises] provision for an independent laboratory of Biochemistry should be made' (Memorandum by the Board of the Faculty of Medicine, 22 Jan 1920, in OUA/HC/1/1/115, pp 47-8), and the letter was referred to a Council committee convened especially to discuss the matter. In March 1920 Edward Whitley, a Liverpool businessman, stated to the Vice-Chancellor that he would add to the sum of £400pa that had been allocated to a new Biochemistry professorship a £10,000 endowment to supplement the stipend of the Professor. The Chair was therefore entitled the 'Whitley Professorship of Biochemistry', with Benjamin Moore becoming the first holder of the Professorship in 1920. The University statute which established the Whitley Chair stated that the Professor should have charge of part of the Physiology Laboratory until an independent laboratory of Biochemistry was provided, as well as providing teaching in both subjects. Rudolph Peters was appointed as the second Whitley Professor in January 1923, Moore having died the previous March.

Peters accepted the Chair on the condition that a department of Biochemistry should be built which was connected physically to Physiology but from which it functioned separately. He was initially allocated the upper floor of the building sufficient for three research workers. Sir Archibald Garrod negotiated with the Rockefeller Foundation about funding for Biochemistry, and eventually £75,000 was offered to the Department in December 1923, with the University having to fund an additional £1250 per annum. There was a site available for building next to 'Old' Physiology. After some more negotiation from Garrod - the site was then in a popular part of the University Parks - the ground was handed over on 9 June 1924. Harry Redfern designed the Biochemistry building, which was built by Wooldridge and Simpson. On 21 October 1927, Viscount Cave officially opened the new department. Biochemistry shared a lecture theatre and library with the Department of Physiology, and these two Departments remained in close physical contact until the 1950s, when their areas of research diverged and they were separated physically.

1935 saw discussions about installing an ultra-centrifuge, which would facilitate the study of large molecules in solutions and enable proteins to be separated by their size and shape. In May of that year, Theodor Svedberg, inventor of the ultra-centrifuge, offered one on loan to Peters, provided the funds could be found to transport, install and maintain it.

The Hebdomadal Council agreed on 10 June 1935 to support its installation and an extension to the Department to accommodate it was begun in 1936, designed by Redfern.

This extension, which amounted to around 7 metres at the end of each corridor on all three floors of the building, additionally provided more research space, allowing the ultra-centrifuge to be installed in 1937.

1945 saw the start of Microbiology in the Department, with the appointment of Donald Woods as a Reader in Microbiology. The consolidation of Biochemistry as a major academic presence in Oxford was furthered by the creation of a new final honour school in Biochemistry in 1949, which meant that Biochemistry could be read as an honours subject in its own right, rather than merely as part of the Physiology honour school, as it had been previously.

In October 1954, the new Whitley Professor, Hans Krebs, and 15 staff moved to Oxford in what would become the Medical Research Council (MRC) unit for Medical Research in Cell Metabolism. Another extension of the Biochemistry Department then became an urgent priority. Krebs' MRC unit was initially housed in concrete huts next to the Biochemistry building, before moving into part of 'old' Physiology. The new Biochemistry extension would be immediately adjacent to 'old' Biochemistry. The Microbiology building was completed in 1960. After its completion, the Tower extension was able to begin, and teaching commenced there in Michaelmas Term 1963. An Open Day was held on 2 May 1964 for Sir Rudolph and Lady Peters, the Wellcome Trustees and members of the public to see the new extension.

Rodney Porter's appointment to the Whitley Professorship after Krebs' retirement in 1967 led to the creation of the Immunochemistry Unit, for which the laboratory on the fourth floor of the Tower was adapted. Porter also urged that a Professorship be established to 'balance' that of Microbiology, and a statute upgrading Ford's Readership in Genetics to a Professorship after Porter's retirement was passed by Hebdomadal Council in July 1968. Walter Bodmer was appointed to the Professorship in July 1969, and was allocated space on the ground floor of 'old' Physiology.

In the same year, Rex Richards, Dr Lee's Professor of Chemistry, was offered space in Biochemistry by Porter for further research into nuclear magnetic resonance (NMR). This led to the formation of the Science Research Council (SRC) Enzyme Group, consisting of senior University staff and their research teams from various departments. Richards agreed to chair the Group, which saw considerable success in the 1970s, although Richards's appointment to the Vice-Chancellorship in 1977 meant that he had less time to devote to it.

As the 1980s and 1990s progressed, a continuing lack of space coupled with the emergence of new Units led to the construction of a number of new buildings. The Rex Richards building, designed by the University Surveyor, Jack Lankester, opened in 1985 to house new laboratories for the Enzyme Group and the Immunochemistry Unit.

The Rodney Porter building was opened in 1991 to house the Glycobiology Institute. That year also saw the establishment of the MRC Chemical and Clinical Magnetic Resonance Unit, the building for which was completed in 1992 to house the first whole-body magnet for human NMR spectroscopy. Towards the end of the 1990s space in the Department was once again becoming a serious issue; the old Biochemistry building's foundations were too weak to take the construction of any further floors, and working conditions in the Tower block were found to be substandard. New funding from the Wolfson Foundation was obtained for a new laboratory, and the destruction of the old Biochemistry, Genetics and old Physiology buildings commenced in summer 2006.

In 2000 the Board of the Faculty of Biological Sciences, under whose jurisdiction Biochemistry had been previously, was abolished and Biochemistry was assigned to the Life and Environmental Sciences Division. In 2006, another structural revision saw Biochemistry allocated to the Medical Sciences Division.

Whitley Professors of Biochemistry: