Born in Rocky Point, North Carolina, Ashe attended school in Fayetteville and pusued classical studied at Trinity College in Hartford, Connecticut. Ashe engaged in rice cultivation and studied law; he was admitted to the state bar in 1836 and practiced in New Hanover County.
Active in the Democratic Party, Ashe was a presidential elector in 1844 and was elected to the North Carolina Senate for a term of two years. (1846-1848). In 1848, he was sent to the U.S. House, serving in the 31st, 32nd, and 33rd Congresses (March 4, 1849 - March 3, 1855). During the 32nd Congress, Ashe chaired the Committee on Elections. He did not run again in 1854, but served as the president of the Wilmington & Weldon Railroad Company from 1854 until his death.
He was elected to one further term in the North Carolina Senate between 1859 to 1861. He was a delegate to the Charleston Democratic National Convention in 1860 and the North Carolina Constitutional Convention of 1861. During the American Civil War, Ashe was a major in the Confederate Army, in charge of all transporation between Virginia and the rest of the South. Ashe was killed in a railroad accident near Wilmington, North Carolina on September 14, 1862. His is buried in a family cemetery in Pender County, North Carolina.
In 1842, Ashe was elected to a single term in the North Carolina House of Commons, from 1847 to 1851 he was solicitor of the fifth judicial district of North Carolina, and in 1854, he served in the North Carolina Senate.
Ashe was still serving on the court at the time of the death in Wadesboro in 1887.
Thomas Samuel Ashe was the cousin of fellow Congressmen John Baptista Ashe and WilliamShepperdAshe.