The issues in the campaign were slavery, the prohibition of alcohol, and the nativist positions of the Know Nothing Party. Johnson favored the first, but opposed the others. Gentry was more equivocal on the alcohol question, and had gained the support of the Know Nothings, a group Johnson portrayed as a secret society.[62] Johnson was unexpectedly victorious, albeit with a narrower margin than in 1853.[63]
When the presidential election of 1856 approached, Johnson hoped to be nominated; some Tennessee county conventions designated him a "favorite son". His position that the best interests of the Union were served by slavery in some areas made him a practical compromise candidate for president. He was never a major contender; the nomination fell to former Pennsylvania senator James Buchanan. Though he was not impressed by either, Johnson campaigned for Buchanan and his running mate, John C. Breckinridge, who were elected.[64]
Johnson decided not to seek a third term as governor, with an eye towards election to the U.S. Senate. In 1857, while returning from Washington, his train derailed, causing serious damage to his right arm. This injury would trouble him in the years to come.