With the outbreak of the Civil War, Weed was promoted captain of the newly formed Battery I, 5th U.S. Artillery in May 1861. He remained at Camp Curtin in Harrisburg, Pennsylvania, training his crews until the spring of 1862, when they served in the Peninsula Campaign and at Second Bull Run. He commanded his battery during the fierce artillery duel at Antietam. Promoted to command of all the artillery of the V Corps, his guns were in action at the Battle of Fredericksburg. From December 1862 through January 1863, he was stationed at Falmouth, Virginia. After a short leave of absence, he took part in the Battle of Chancellorsville, commanding the artillery of the 2nd Division, V Corps. On June 6, 1863, Weed left the regular army artillery to accept a commission as a brigadier general in the volunteer army. He was assigned command of 3rd Brigade in the 2nd Division, V Corps.