In May 1861, Warren received his appointment as lieutenant colonel of the 5th New York Infantry. A month later, he saw action at the Battle of Big Bethel Church. He was soon elected colonel of his regiment. During the Peninsula campaign, he was wounded at the Battle of Gaines' Mills. He soon returned to the field in command of a brigade. He saw action at the Battle of Second Manassas, and subsequently, at the Battle of Antietam. He was promoted to brigadier general less than two weeks later. In the following spring, he rose to the rank of major general. At the Battle of Gettysburg, he served as the chief engineer of the Army of the Potomac. In August 1863, he temporarily took command of the II Corps. In March 1864, he received permanent command of the V Corps going into the Overland campaign under orders from General Ulysses S. Grant. However, at the Battle of Five Forks, Philip Sheridan relieved Warren of his command, which ended his career.