Born in Dodge Center, Minnesota, Humason had no formal university training – in fact he began work as a donkey driver moving supplies to the Mount Wilson Observatory in southern California. Here he quickly developed an interest in astronomy and its techniques, an interest that was stimulated by the staff of the observatory. He was taken on as janitor and by 1919 he was competent enough to be appointed assistant astronomer on the staff of the Mount Wilson Observatory and, after 1948, of the Palomar Observatory, where he spent the rest of his career.

In the 1920s Edwin Hubble formulated his law that the distance of the galaxies was proportional to their recessional velocity. This work was based on the careful, painstaking, and difficult measurements of galactic red shifts made by Humason and also by Vesto Slipher. Humason developed extraordinary skill in this field. By 1936, using long photographic exposures of a day or more, he was able to measure a recessional velocity of 40,000 kilometers per second, which took him to the limits of the 100-inch (2.5-m) reflecting telescope at Mount Wilson.

With the opening of the Palomar Observatory he was able to use the 200-inch (5-m) Hale reflector and by the late 1950s was obtaining velocities of over 100,000 km per second; this corresponded to a distance, according to Hubble's law, of about six billion light-years.