He was a partner with Fowler & Wells, publishers, New York, from 1846 to 1854, residing in Fishkill, New York, and Elizabeth, New Jersey. Orson edited and published The American Phrenological Journal and Miscellany, Philadelphia, Pennsylvania, from 1838 to 1842.
For instance, in "Hereditary Descent" (1843), Fowler wrote that Jewish people were hereditarily acquisitive, deceitful, and destructive (phrenology believes that none of these "organs" are negative as such, but all can be used for good). At the same time, the phrenological journal edited by Fowler and his brother expressed strong abolitionist sentiments, calling slavery a "a monstrous evil." Fowler's writings were also anti-Semitic. Fowler wrote that coarse hair correlated with coarse fibers in the brain, and indicated coarse feelings that, he wrote, suggested that people of African descent had poor verbal skills and traits that were best suited for nursing children or waiting on tables. The practice of phrenology was frequently used to justify slavery and to advance a belief in African-American inferiority. The three were "in large measure" responsible for the mid-19th century popularity of phrenology. Lorenzo and his wife Lydia Folger Fowler lectured frequently with Orson on the subject of phrenology. Orson wrote and lectured on phrenology, preservation of health, popular education and social reform from 1834 to 1887. With his brother Lorenzo Niles Fowler, he opened a phrenological office in New York City. The son of Horace and Martha (Howe) Fowler, he was born in Cohocton, New York, He prepared for college at Ashland Academy and studied at Amherst College, graduating in the class of 1834.
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