Edward Cross was born in Hawkins County, Tennessee, and he attended public schools during his youth. He studied law and was admitted to the bar. In 1826 he moved to Arkansas and was appointed as a federal judge for the Territory of Arkansas on 26 May 1830. From 30 April 1836 to 1 September 1838 he served as United States surveyor general for Arkansas.
Cross was elected as a Democrat to the Twenty-sixth, Twenty-seventh, and Twenty-eighth United States Congresses between 4 March 1839 and 3 March 1845.
During the Twenty-eighth Congress he served as chairman of the Committee on Private Land Claims. He served as a justice of the Arkansas Supreme Court from July 1845 to 1855. Cross served as president of the Cairo & Fulton Railway (later the St. Louis, Iron Mountain and Southern Railway from 1855 to 1862. In 1874 he was appointed attorney general of Arkansas.
Edward Cross died at his residence, Marlbrook, near Washington, Hempstead County, Arkansas on 6 April 1887. Cross was buried at his residence. His remains were moved to the Marlbrook Cemetery near modern day Blevins Arkansas in the 20th century.
Cross County, Arkansas is named for his son David Cross.
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