Upton was commissioned a second lieutenant in the 4th U.S. Artillery, transferring to the 5th U.S. Artillery as a first lieutenant on May 14, assigned to Brig. Gen. Irvin McDowell's Army of Northeastern Virginia, as an aide-de-camp to Brig. Gen. Daniel Tyler. In the First Battle of Bull Run, July 21, 1861, he was wounded in the arm and left side during the action at Blackburn's Ford, although he did not leave the field. He commanded his battery in the VI Corps Artillery Reserve through the 1862 Peninsula Campaign and the Seven Days Battles. In the Maryland Campaign, including the battles at Crampton's Gap at South Mountain and the Battle of Antietam, he commanded the artillery brigade for the 1st Division, VI Corps.