Born in St. Paul, Minnesota, Calvin studied chemistry at the Michigan College of Mining and Technology and gained his BS degree in 1931. After obtaining his PhD from the University of Minnesota in 1935 he spent two years at Manchester working with Michael Polanyi. Here he became interested in chlorophyll and its role in the photosynthetic process in plants. Calvin began a long association with the University of California at Berkeley in 1937. From 1941 to 1945 he worked on scientific problems connected with the war, including two years on the Manhattan Project (the atomic bomb).

In 1946 Calvin became director of the Bio-organic Division of the Lawrence Radiation Laboratory at Berkeley, where he used the new analytical techniques developed during the war – ion-exchange chromatography, paper chromatography, and radioisotopes – to investigate the ‘dark reactions’ of photosynthesis, i.e. those reactions that do not need the presence of light. Plant cells were allowed to absorb carbon dioxide labeled with the radioisotope carbon–14, then immersed at varying intervals in boiling alcohol so that the compounds they synthesized could be identified. In this way the cycle of photosynthetic reactions (known as the Calvin cycle) was elucidated and shown to be related in part to the familiar cycle of cell respiration. This work, which was collected in The Path of Carbon in Photosynthesis (1957), earned Calvin the Nobel Prize for chemistry in 1961.

Calvin remained at Berkeley, as director of the Laboratory of Chemical Biodynamics (1960–63), professor of molecular biology (1963–71), and professor of chemistry (1971). He continued to work on problems of photosynthesis (especially on the role of chlorophyll in quantum conversion) and on the evolution of photosynthesis.