He enlisted in 1861 in the Union army in an Irish-American three-months regiment, the 24th Pennsylvania, and quickly made a captain. He was later commissioned as major of the 1st Delaware Infantry, a three-years regiment. He served at the battles of Fredericksburg (following which he was promoted to lieutenant colonel and then to colonel) and Chancellorsville. During the Gettysburg Campaign, he commanded the 2nd Brigade, 3rd Division of the II Corps. During the Battle of Gettysburg, his men helped defend Cemetery Ridge and advanced to the area of the Bliss farm to oust enemy sharpshooters. Smyth was wounded on the third day of the battle and relinquished command briefly.