In 1861, Humphreys was assigned to serve with the Topographical Engineers as a major. In 1862, he was assigned to the Army of the Potomac, and he received his promotion to brigadier general. In 1863, he was given a promotion to chief of staff to the Army of the Potomac as a major general. He served at Yorktown, Williamsburg, Seven Days', Fredericksburg, Chancellorsville, and Gettysburg. In his role as chief of staff, he served through the Bristoe, Mine Run, Overland, and Petersburg campaigns. He musters out in 1866.