After returning to the U.S., he began a career in Astronomy that culminated when he became director of the Mount Wilson Observatory.

He worked on solar spectroscopy and co-discovered a relationship between the relative intensities of certain spectral lines and the absolute magnitude of a star.

In 1915 he began a study of the companion of Sirius and found that despite a size only slightly larger than the Earth, the surface of the star was brighter per unit area than the Sun and it was about as massive.

In 1925, he reported a gravitational redshift caused by Sirius B; this was regarded as significant confirmation of Albert Einstein's theory of General Relativity.

Along with Theodore Dunham, he discovered the strong presence of carbon dioxide in the infrared spectrum of Venus.