Slipher was born in Mulberry, Indiana, and completed his doctorate at Indiana University in 1909. He spent his entire career at Lowell Observatory in Flagstaff, Arizona, where he was promoted to assistant director in 1915, acting director from 1916, and finally director from 1926 until his retirement in 1952. He used spectroscopy to investigate the rotation periods of planets, the composition of planetary atmospheres. In 1912, he was the first to observe the shift of spectral lines of galaxies, so he was the discoverer of galactic redshifts. He was responsible for hiring Clyde Tombaugh and supervised the work that led to the discovery of Pluto in 1930.
Edwin Hubble was generally incorrectly credited with discovering the redshift of galaxies; these measurements and their significance were understood before 1917 by James Edward Keeler (Lick & Allegheny), Vesto Melvin Slipher (Lowell), and William Wallace Campbell (Lick) at other observatories.
Combining his own measurements of galaxy distances with Vesto Slipher's measurements of the redshifts associated with the galaxies, Hubble and Milton Humason discovered a rough proportionality of the objects' distances with their redshifts. Though there was considerable scatter (now known to be due to peculiar velocities), Hubble and Humason were able to plot a trend line from the 46 galaxies they studied and obtained a value for the Hubble-Humason constant of 500 km/s/Mpc, which is much higher than the currently accepted value due to errors in their distance calibrations. Such errors in determining distance continue to plague modern astronomers (See cosmic distance ladder for more details).
In 1929 Hubble and Humason formulated the empirical Redshift Distance Law of galaxies, nowadays termed simply Hubble's law, which, once the redshift is interpreted as a measure of recession speed, is consistent with the solutions of Einstein’s General Relativity Equations for a homogeneous, isotropic expanding space de Sitter universe or de Sitter space. Although concepts underlying an expanding universe were well understood earlier, this statement by Hubble and Humason lead to wider scale acceptance for this view. The law states that the greater the distance between any two galaxies, the greater their relative speed of separation.
This discovery later resulted in formulation of the Big Bang theory by George Gamow, a consequence of the observed velocities of distant galaxies that when taken together with the cosmological principle imply that space is expanding according to the Friedmann-Lemaître model of general relativity.
He died in Flagstaff, Arizona and is buried there in Citizens Cemetery.