Frederick Steidinger Heiskell was born in 1786, the son of Frederick and Catherine (Steidinger) Heiskell. When he was a child, his parents moved from western Maryland to Shenandoah County, Virginia. He learned the printer's trade in the office of his brother, John Heiskell, in Winchester, Virginia, and then moved to Knoxville in December 1814. After working as a journeyman printer for two years, he established the Knoxville Register in 1816, in partnership with Hugh Brown, his brother-in-law. On July 17, 1816, he married Eliza Brown, daughter of Joseph Brown, an early Washington County sheriff. In 1836, Frederick Heiskell sold the Register to Col. W. B. A. Ramsey and Robert Craighead and moved to a large farm ten miles west of Knoxville that he named Fruit Hill. Frederick Heiskell was active in politics, being elected to the Tennessee Senate for three terms. His correspondents included Andrew Jackson, Felix Grundy, Hugh Lawson White, John Bell, and many other political leaders. Heiskell served on the Knoxville Board of Mayors and Aldermen from 1825 until 1831. He served as mayor for a brief period in 1835.

Heiskell had many other interests beyond politics. He became a tireless campaigner for public education and civic improvement, backing his editorial support with service on countless boards and commissions. Heiskell was one of the founders, and for many years treasurer, of the Knoxville Public Library. He served as a trustee of the Knoxville Female Academy and its successor, the East Tennessee Female Institute, from 1827 until his death in 1882. He was also a trustee of East Tennessee College, now the University of Tennessee.

His wife died on November 10, 1851, and he then married Mrs. Alice Gale (Armstrong) Fulkerson of Rogersville, July 21, 1853. Alice died in 1874, whereupon Heiskell moved back to Knoxville and finally to Rogersville where he died in 1882.