He was born in Elizabeth City County, Virginia, attended Hampton Academy and was appointed midshipman in the United States Navy where he served 1822-1828. Dr, Mallory was graduated from the medical department of the University of Pennsylvania at Philadelphia in 1831 and practiced in Norfolk, Virginia.

Dr. Mallory served as a Representative in the U.S. Congress, as a Delegate in the Virginia General Assembly, and as a Navy Agent in Norfolk appointed by President Millard Fillmore.

For may years, he helped lobby before the State Legislature for a railroad line to Norfolk and was opposed by shipping interests from Richmond and Petersburg. In 1851, the Norfolk interests finally succeeded in obtaining a charter and financing from the Virginia Board of Public Works to form the Norfolk and Petersburg Railroad (N&P). In 1853, the new railroad hired a 26-year old civil engineer and graduate of Virginia Military Institute from Southampton County by the name of William Mahone. Small-statured "Little Billy" Mahone was frugal with expenses while he built the N&P to high construction standards. Mahone is credited with the design and implementation of an innovative roadbed through the Great Dismal Swamp near Norfolk, Virginia, employed a log foundation laid at right angles beneath the surface of the swamp. Still in use today, Mahone's design withstands immense tonnages of coal traffic. He was also responsible for engineering and building the famous 52 mile-long tangent track between Suffolk and Petersburg which is a major artery of modern Norfolk Southern rail traffic.

Dr. Mallory survived the Yellow Fever Epidemic which swept through Norfolk in 1855 and killed 2,000 of its 6,000 citizens. However, construction of his new railroad was delayed for more than a year due to the many deaths and resulting financial hardships. After the railroad was completed in 1858, he stepped down and Mahone became its new president.

Dr. Mallory died in Norfolk on March 26, 1860, and was buried in Elmwood Cemetery there.