John A. Wilcox was born in Greene County, North Carolina, on April 18, 1819, to Reuben Wilcox and Sarah Garland. The family moved to Mississippi during his childhood, and he served as secretary of the state senate. He served as lieutenant colonel of the 2nd Mississippi Infantry during the Mexican-American War. After the war, he practiced law in Aberdeen, Mississippi, and he was elected to Congress as a Whig in 1850. He moved to Texas in 1853 and joined the Democratic Party in 1858.

Wilcox served in the Texas Secession Convention and helped draft the state's ordinance of secession. He was elected to the Confederate Congress in November 1861 and became a staunch supporter of Confederate President Jefferson Davis. Wilcox joined the Confederate army after his term expired, serving as an aide to Major General John B. Magruder. He died in Richmond, Virginia, on February 7, 1864.