Tilton enlisted in the army and became a first lieutenant in the 22nd Regiment Massachusetts Volunteer Infantry on September 12, 1861.

Tilton was made colonel of the 22nd Massachusetts Infantry on October 17, leading the regiment at the Battle of Fredericksburg.

In 1863, Tilton continued leading the regiment in the First Brigade, First Division, under Barnes, who had recently become a brigadier general, including at the Battle of Chancellorsville.

His command was deployed on the right flank of Col. Jacob B. Sweitzer's 2nd Brigade in between the Peach Orchard and the Wheatfield on July 2, 1863.

[1] Whatever the truth of this, Tilton said he reconnoitered and discovered a large Confederate force coming up on his left flank.

Another estimate is that Tilton lost 125 of 655 men, a loss of 19.1%, a low percentage compared to Sweitzer's 30% reported by the same author.

When the Army of the Potomac was reorganized in 1864 for Lt. Gen. Ulysses S. Grant's Overland Campaign, Tilton was assigned to lead his regiment in Jacob Sweitzer's brigade of Griffin's division.

On December 12, 1864,[3] President Abraham Lincoln nominated Tilton for the award of the honorary grade of brevet brigadier general, United States Volunteers, to rank from September 9, 1864, for distinguished services during the war.