The first endeavor of Sterling Price into public service was in Missouri, where he served first in the Missouri House of Representatives and then the United States Congress, up until the outbreak of the Mexican-American War. Once the war started, Price resigned from Congress, was appointed colonel of the Second Missouri, and became the military governor of New Mexico. While he was military governor, Price put down a rebellion of Native Americans and Mexicans, known as the Taos Revolt, and fought the last battle of the Mexican-American War, the Battle of Santa Cruz de Rosales, after the war had technically ended. He returned to Missouri after the war, and was elected governor of the state from 1853 to 1857. In March of 1861, Price was president of the Missouri convention that opposed secession, but as a result of disagreements he had with Unionists, Price accepted command of the Missouri Militia to fight for the Confederacy.
He commanded the Missouri Militia at the battle of Wilson’s Creek, where he helped to defeat Union General Nathaniel Lyon, at the First Battle of Lexington, as well as at the Battle of Pea Ridge. After the Battle of Pea Ridge, Price was granted a commission in the Confederate army on March 6, 1862 as a major general, and the Missouri Militia were added to the Confederate Army of the West. He then led his men in a campaign around Iuka and Corinth, Mississippi, in 1862, and was defeated at the Battle of Helena in Arkansas. In 1864, he led an expedition back into Missouri with initial success, but was defeated at the battles of Westport and Mine Creek. He fled with his army to Texas, and then into Mexico where they stayed until after the Civil War had ended.