Seth Barnes Nicholson was born in 1891. He was raised in Illinois and became interested in astronomy as an undergraduate at Drake University. Using the famous 36-inch Crossley Reflector, he photographed the recently-discovered eighth moon of Jupiter and made a discovery of a ninth moon. Nicholson was a graduate student at the University of California at the time, and computed the orbit of his discovery for his Ph.D. dissertation.

He spent his entire career at Mt. Wilson Observatory, where he discovered a Trojan asteroid and three more of Jupiter's moons using the 100-inch Telescope. Nicholson computed the orbits of several comets and of Pluto, and for decades produced annual reports on sunspot activity and magnetism from his observations with the 150-foot Solar Tower Telescope.

In the early 1920's, Seth Nicholson and Edison Pettit used a vacuum thermocouple to measure the temperatures of the Moon, planets, sunspots, and stars. Their temperature measurements of nearby giant stars led to some of the first determinations of stellar diameters. Nicholson also made a number of eclipse expeditions to measure the brightness and temperature of the solar corona.