In January 1861 Coke was elected as a delegate to the Texas Secession Convention, representing McClennan and Bosque Counties. When the Civil War broke out, Coke volunteered as a private in the Confederate Army, formed a company of infantry soldiers, and eventually rose to Captain of Company K, 15th Texas Infantry. He was wounded at Bayou Bourbeau (Muddy Creek), near Opelousas, Louisiana, on November 3, 1863 but eventually returned to service until war's end. When Coke was discharged from the Confederate Army in May 1865 he returned to his family and his law practice in Waco.

On September 1, 1865 Coke was appointed district judge of the Nineteenth Judicial District by Provisional Governor A. J. Hamilton. In August 1866 he was elected to the Texas Supreme Court. He served until being ousted along with Governor Throckmorton by General Philip Sheridan, the commander of Texas under military rule. Sheridan's action cost Coke his job, but gained for Coke the endearment of a large majority of Texans. Coke's popularity became abundantly evident in the gubernatorial election in 1873, when he defeated incumbent E. J. Davis by a margin of two to one.

As governor, Coke turned his attention to education and tax reform, established a funding system for schools, and assisted in opening Texas A&M University. For this role, he is often credited as the father of Texas A&M. Frontier security was also a major concern. He sent forces to the border to protect Texans from marauding Mexican bandits, and he also enlisted federal help with Indian problems and organized troops in areas where Indian raids were frequent. He was reelected governor in February 1876, but was elected by the state legislature to the U.S. Senate later that year. He served eighteen years in the U.S. Senate before retiring due to ill health in 1894. He returned to Waco, where he died at his home on May 14, 1897. He was buried in Oakwood Cemetery in Waco.