When the Mexican War broke out, he enlisted in George Wood's Second Regiment of the Texas Mounted Volunteers. He was so impressive during this time that he was promoted to major in July of 1846. After the war, he married Janette Sutton, returned to his law practice and ran the Austin State Gazette until 1854.

After Texas had decided to side with the Confederate cause during the Civil War, Scurry enlisted as a lieutenant colonel of the Fourth Texas Cavalry. His military skills had not diminished since his time in the Mexican War, distinguishing himself at the Battle of Glorieta and the invasion of New Mexico. He was promoted to brigadier general on September 12, 1862 and continued his exceptional work in the CSA, playing a key role in the recapture of Galveston in early 1863. He was assigned to command the Third Brigade of Walker's Texas Division in October 1863 and led his men at the Battles of Mansfield and Pleasant Hill in early April 1864, then was given orders to repel the Union soldiers marching towards northeast Texas. Met them he did, on April 30, 1864, at the Battle of Jenkins Ferry. He was wounded in the leg during the battle, but refused to be carried to the rear, fearing that to do so would cause his troops to lose the morale needed to turn the enemy. When the Union soldiers overwhelmed the Confederates, his injury was forgotten for over two hours while the battle was fought around him; by the time his men had pushed them back, he was near death. After he was found, he asked "Have we whipped them?" Once he was assured that his men had been victorious, he asked to be moved to a house so that he could "be made comfortable and die easy." General William Read Scurry was buried with full military honors at the Texas State Cemetery. Within a few years, Scurry County was named in his honor.