This brought Zollicoffer into political circles, and he was Comptroller of the State Treasury from 1845 to 1849, as well as Adjutant General for the state. He was a member of the State Senate from 1849 until 1852, and was a delegate to the Whig National Convention in 1852, supporting General Winfield Scott. Zollicoffer was himself elected as a Whig to the Thirty-third United States Congress and was reelected as a candidate of the American Party to the Thirty-fourth and Thirty-fifth Congresses (March 4, 1853 – March 3, 1859). During his first campaign, he fought a duel with the editor of the rival "Nashville Union" newspaper. He declined to be a candidate for renomination in 1858 and retired to private life. He supported fellow Tennessee moderate John Bell (CU) for president in the election of 1860.