He was the son of well-known parents: his father, James Iredell, was a statesman and U.S. Supreme Court justice, and his mother was the sister of former Governor Samuel Johnston.

On his way toward political prominence, Iredell commanded a company of volunteers during the War of 1812, practiced law in Chowan County, served in the state House of Commons, as a representative from Edenton, and was appointed a Superior Court judge.

However, his brief time in office (and the inherent weaknesses of the governor under the Constitution of North Carolina) did not allow him to accomplish much.

[citation needed] He left office after a few months to serve in the U.S. Senate, a post he held from 1828 to 1831.

Iredell did not seek to be re-elected by the state General Assembly to a full term in the Senate.