Edwin Hubble was born to Virginia Lee Hubble (née James) (1864–1934) and John Powell Hubble, an insurance executive, in Marshfield, Missouri, and moved to Wheaton, Illinois, in 1900. In his younger days, he was noted more for his athletic prowess than his intellectual abilities, although he did earn good grades in every subject except for spelling. Edwin was a gifted athlete playing baseball, football, basketball, and he ran track in both high school and college. He played a variety of positions on the basketball court from center to shooting guard. In fact Hubble even led the University of Chicago's basketball team to their first conference title in 1907. He won seven first places and a third place in a single high school track and field meet in 1906.

Hubble discovered that many objects previously thought to be clouds of dust and gas and Classified as "nebulae" were actually galaxies beyond the Milky Way. He used the strong direct relationship between a classical Cepheid variable's luminosity and pulsation period (discovered in 1908 by Henrietta Swan Leavitt) for scaling galactic and extragalactic distances.

In 1909, Hubble's Father moved his family from Chicago to Shelbyville, Kentucky, so that the family could live in a small town, ultimately settling in nearby Louisville. His Father died in the winter of 1913, while Edwin was still in England, and in the summer of 1913, Edwin returned to care for his mother, two sisters, and younger brother, as did his brother william. The family moved once more to Everett Avenue, in Louisville's Highlands neighborhood, to accommodate Edwin and william.

His studies at the University of Chicago were concentrated on law, which led to a bachelor of science degree in 1910. Hubble also became a member of the Kappa Sigma Fraternity. He spent the three years at The Queen's College, Oxford after earning his bachelors as one of the university's first Rhodes Scholars, initially studying jurisprudence instead of science (as a promise to his dying father), and later added literature and Spanish, and earning his master's degree.

Hubble was also a dutiful son, who despite his intense interest in astronomy since boyhood, acquiesced to his father's request to study law, first at the University of Chicago and later at Oxford, though he managed to take a few math and science courses. After the death of his Father in 1913, Edwin returned to the Midwest from Oxford, but did not have the motivation to practice law. Instead, he proceeded to teach Spanish, physics and mathematics at New Albany High School in New Albany, Indiana, where he also coached the boys' basketball team. After a year of high-school teaching, he entered graduate school with the help of his former professor from the University of Chicago to study astronomy at the university's Yerkes Observatory, where he received his PhD in 1917. His dissertation was titled "Photographic Investigations of Faint Nebulae". In Yerkes, he had access to one of the most powerful telescopes in the world at the time, which had an innovative 24 inch (61 cm) reflector.

After the United States declared war on Germany in 1917, Hubble rushed to complete his PhD dissertation so he could join the military. Hubble volunteered for the United States Army and was assigned to the newly created 86th Division, where he served in 2nd Battalion, 343 Infantry Regiment. He rose to the rank of lieutenant colonel, and was found fit for overseas duty on July 9, 1918, but the 86th Division never saw combat. After the end of World War I, Hubble spent a year in Cambridge, where he renewed his studies of Astronomy. In 1919, Hubble was offered a staff position at the Carnegie Institution for Science's Mount Wilson Observatory, near Pasadena, California, by George Ellery Hale, the founder and Director of the observatory. Hubble remained on staff at Mount Wilson until his death in 1953. Shortly before his death, Hubble became the first Astronomer to use the newly completed giant 200-inch (5.1 m) reflector Hale Telescope at the Palomar Observatory near San Diego, California.

Edwin Hubble's arrival at Mount Wilson Observatory, California in 1919 coincided roughly with the completion of the 100-inch (2.5 m) Hooker Telescope, then the world's largest. At that time, the prevailing view of the cosmos was that the universe consisted entirely of the Milky Way Galaxy. Using the Hooker Telescope at Mt. Wilson, Hubble identified Cepheid variables (a kind of star that is used as a means to determine the distance from the galaxy – see also standard candle) in several spiral nebulae, including the Andromeda Nebula and Triangulum. His observations, made in 1922–1923, proved conclusively that these nebulae were much too distant to be part of the Milky Way and were, in fact, entire galaxies outside our own, suspected by researchers at least as early as 1755 when Immanuel Kant's General History of Nature and Theory of the Heavens appeared. This idea had been opposed by many in the astronomy establishment of the time, in particular by Harvard University-based Harlow Shapley. Despite the opposition, Hubble, then a thirty-five-year-old scientist, had his findings first published in The New York Times on November 23, 1924, and then more formally presented in the form of a paper at the January 1, 1925 meeting of the American Astronomical Society.

In 1929, in his first published paper, Hubble examined the relation between distance and redshift of galaxies. Combining his measurements of galaxy distances with measurements of the redshifts of the galaxies by Vesto Slipher, and by his assistant Milton L. Humason, he found a roughly linear relation between the distances of the galaxies and their redshifts, a discovery that later became known as Hubble's law.

In the 1930s, Hubble was involved in determining the distribution of galaxies and spatial curvature. These data seemed to indicate that the universe was flat and homogeneous, but there was a deviation from flatness at large redshifts. According to Allan Sandage,

Yet the reason for the redshift remained unclear. Georges Lemaître, a Belgian Catholic priest and Physicist, predicted on theoretical grounds based on Einstein's equations for General Relativity the redshift-distance relation, and published observational support for it, two years before the discovery of Hubble's law. However, many Cosmologists and astronomers (including Hubble himself) failed to recognize the work of Lemaître; Hubble remained doubtful about Lemaître's interpretation for his entire life. In 1931 he wrote a letter to the Dutch cosmologist Willem de Sitter expressing his opinion on the theoretical interpretation of the redshift-distance relation:

There were methodological problems with Hubble's survey technique that showed a deviation from flatness at large redshifts. In particular, the technique did not account for changes in luminosity of galaxies due to galaxy evolution. Earlier, in 1917, Albert Einstein had found that his newly developed theory of general relativity indicated that the universe must be either expanding or contracting. Unable to believe what his own equations were telling him, Einstein introduced a cosmological constant (a "fudge factor") to the equations to avoid this "problem". When Einstein learned of Hubble's redshifts, he immediately realized that the expansion predicted by General Relativity must be real, and in later life he said that changing his equations was "the biggest blunder of [his] life." In fact, Einstein apparently once visited Hubble and tried to convince him that the universe was expanding. Hubble also discovered the asteroid 1373 Cincinnati on August 30, 1935. In 1936 he wrote The Observational Approach to Cosmology and The Realm of the Nebulae which explained his approaches to extra-galactic astronomy and his view of the subject’s history.

In December 1941, Hubble reported to the American Association for the Advancement of Science that results from a six-year survey with the Mt. Wilson telescope did not support the expanding universe theory.

(Note that the assertion that he would have won the Nobel Prize in 1953 is likely false, although he was nominated for the prize that year.)

On March 6, 2008, the United States Postal Service released a 41-cent stamp honoring Hubble on a sheet titled "American Scientists" designed by Artist Victor Stabin. His citation reads:

In November 2011, the Astronomer Mario Livio reported in Nature that documents in the Lemaître archive demonstrated that the redaction had indeed been carried out by Lemaître himself, who apparently saw little point in including scientific content which had already been reported by Hubble.

At the time, the Nobel Prize in Physics did not recognize work done in astronomy. Hubble spent much of the later part of his career attempting to have astronomy considered an area of physics, instead of being its own science. He did this largely so that astronomers—including himself—could be recognized by the Nobel Prize Committee for their valuable contributions to astrophysics. This campaign was unsuccessful in Hubble's lifetime, but shortly after his death, the Nobel Prize Committee decided that astronomical work would be eligible for the physics prize. However, the prize is not one that can be awarded posthumously.