Solon I. Bailey studied at Boston University, obtaining a Bachelor of Arts degree in 1881 and a Master of Arts degree in 1884. From 1881 he was headmaster of Tilton Academy in Concord, New Hampshire, and in 1883 married Ruth E. Poulter, with whom he had two sons. Moving to Harvard University in 1887 he was awarded a second Master's degree in 1888, having qualified in astronomy. In 1888 he was sent to Peru to test climatic conditions for the establishment of a southern station for Harvard College Observatory. He examined the west coast of South America from the equator to southern Chili, eventually recommending Arequipa in southern Peru. His search for a site was described in a lengthy paper, "History of the first Peruvian expedition, 1889-1891", in the Annals of Harvard College Observatory (1893). Bailey was put in charge of the observatory at Arequipa in 1892. He established a chain of meteorological stations in Peru, including the highest meteorological station in the world near Arequipa, at an elevation of 6000 m. His astronomical observations in Peru led to the publication of A catalogue of 7922 southern stars observed with the meridian photometer during the years 1889-1891 (Cambridge, Mass., 1895).
He was appointed assistant professor of astronomy at Harvard University in 1893, was promoted to associate professor in 1898, and served as professor from 1913 until his retirement in 1925. During 1919-1922 he was also acting director of Harvard Observatory. His research included the discovery, in 1895, of Cepheid variable stars with very short periods in the globular cluster Messier 5. The results of his search for variable stars in the clusters Messier 3, 5, and 15 were published in 1913, 1917 and 1919 respectively. He was also a pioneer in the photography and discovery of distant galaxies and published "A catalogue of bright clusters and nebulae", in the observatory's Annals (1908).
In 1908 an expedition under Bailey's direction was sent to South Africa by Harvard College to investigate the interior plateau of the country and select a suitable new site for its southern station in Chili. Bailey inspected the country as far north as Bulawayo, Zimbabwe, and selected three promising sites to conduct observations. The main site was near Hanover in the Karoo, where a small observatory was set up in February 1909. It contained 200 mm and 130 mm visual telescopes and a small photographic instrument. Observations were also made at Bloemfontein and Worcester. The work was described in a semi-popular article, "An expedition to South Africa", in Harvard Graduates' Magazine for December 1908. At the 1909 meeting of the South African Association for the Advancement of Science in Bloemfontein Bailey read a paper on "The search for an ideal astronomical site" (Report, 1909, p. 143). After the completion of his investigations he recommended a site near Bloemfontein. However, no action was taken at the time and Harvard's Boyden Obsevatory southern station was moved there from Peru only in 1926. Bailey received an honorary Doctor of Science degree and was made an honorary professor of astronomy at the University of San Augustin, Peru, in 1923. He was a member of numerous scientific societies in the United States and other countries.