Upon the outbreak of the Mexican–American War in 1846, Campbell answered Tennessee Governor Aaron V. Brown's call for volunteers. He was elected colonel of the First Regiment Tennessee Volunteers on June 3, 1846, and arrived with his regiment in Texas the following month. At the Battle of Monterrey later that year, this company lost one-third of its men in an assault on the town's citadel, earning the nickname, the "Bloody First." Campbell's company also saw action at the Siege of Veracruz and the Battle of Cerro Gordo in 1847.