Orson Ferguson Whitney was born in Salt Lake City, Utah, on Sunday, July 1, 1855. His father, Horace Kimball Whitney, was the eldest son of Newel Kimball Whitney, the second presiding bishop of the Church of Jesus Christ of Latter-day Saints. His mother, Helen Mar Whitney, was the eldest daughter of Heber Chase Kimball, one of the original Twelve Apostles and later a member of the First Presidency of the Church of the Latter-day Saints.

Early in Orson F. Whitney's life, he was educated in the common schools of Salt Lake City and worked for the Union Pacific Railroad. Thereafter, he attended the University of Deseret, now the University of Utah. His final year at the university (1873—1874) was followed by a one-year mission for the Church of the Latter-day Saints in October of 1876. During the spring of 1877, Elder Whitney went alone to northern Ohio, preaching, baptizing, studying the gospel, and writing for the Salt Lake Herald. Whitney returned to Utah in the spring of 1878, arriving home on the first day of April. Two weeks later he was employed by the Deseret News. In August of 1878, he was promoted to city editor of the Deseret News.

On July 14, 1878, Orson F. Whitney was made bishop of the Salt Lake City 18th Ward. During that winter (1878—1879), Bishop Whitney went on a preaching tour of Cache Valley, Utah. In the fall of the following year, on December 18, 1879, Whitney married Miss Zine Beal Smoot of Provo, Utah. Over the course of their twenty-year marriage, Zine bore Orson nine children; Horace Newel (1880), Emily (1885), Helen Margaret (1887), Margaret (1889), Charles Byron (1891), Albert Owen (1893), the twins—Paul Van Cott and Virginia Clayton (1899), and Heber Kimball (1899).

In February of 1880, a year-and-a half after their marriage, Orson F. Whitney was called on a church mission to Europe to labor in the editorial department of the Millennial Star in Liverpool. While on this mission, Whitney's second son, Heber Kimball (whom he had never seen), died. Whitney labored in England for three-and-a-half years until his return home to Salt Lake City on July 7, 1883.

Upon his return, Whitney resumed his position at the Desert News, but he later resigned in December of 1884 to become the city treasurer. He was reelected every two years until 1890. During this time, and perhaps in secret, on July 24, 1888, in Colonia Diaz, Mexico, Orson took a second wife by marrying Mary Minerva Wells of Salt Lake City. Residing together at various time in Logan, Utah, they had two children; Murray Wells (1892) and Wendell Webb (1895). In 1896 Whitney accepted the chair of philosophy at Brigham Young College in Logan, were he resided until July of 1897. On May 20, 1900, at the age of 41, Zine Beal Smoot Whitney died, leaving eight children in the care of her husband and his second wife Mary. Later that year, on October 11, 1900, Orson and Mary were remarried in the Salt Lake Temple. In 1901 Orson sat in legislature pushing for the adoption of the Evan's Bill. In 1907 Orson was ordained a member of the Quorum of the Twelve Apostles, a high calling within the Latter-day Saints Church. Thereafter, his spiritual profession required him to travel a great deal, often to various towns and cities across the United States.

Over the course of Orson's public career, he published many articles and books, among them Baptism—The Birth of Water and of Spirit, The Strength of the Mormon Position, Voices from the Mountains, Gospel Themes: a Treatise on Salient Features of Mormons, Popular History of Utah, History of Utah, The Life of Heber C. Kimball, and Through Memory’ Halls: The Life Story of Orson F. Whitney. In addition to publishing, during the 1920s Orson delivered spiritual lectures that were broadcast live on Sunday evenings over KSL Radio, Salt Lake City.

On May 16, 1931, Orson F. Whitney died at the age of 76. Mary M. Whitney died four years later on January 25, 1935.