Meyerhof was born in Hannover as the son of wealthy Jewish parents. He spent most of his childhood in Berlin, where he later started studying medicine. He continued these studies in Straßburg and Heidelberg, and graduated in 1909, with a work titled "Contributions to the phychological Theory of mental illness". In Heidelberg, he met Hedwig Schallenberg, who later became his wife. They had a daughter and two sons.

In 1912, he moved to the University of Kiel, where he became professor in 1918. In 1922, he was awarded the Nobel Prize in Medicine, together with Archibald Vivian Hill, for his work about muscle metabolism, including glycolysis. Fleeing the Nazi regime, he moved to Paris in 1938, then to the U.S. in 1940, where he became a guest professor at the Pennsylvania University im Philadelphia.