Burnside, a graduate of the U.S. Military Academy at West Point, N.Y. (1847), resigned his commission in 1853 and for the next five years manufactured firearms at Bristol, R.I. Soon after the Civil War broke out, Burnside took command of a Rhode Island militia regiment. He was later commissioned a brigadier general in the Union Army and fought in the North Carolina coast campaign. Promoted to major general (1862), he was transferred to the Virginia theatre of war. In command of General George McClellan's left wing at the Battle of Antietam (Antietam, Battle of), Md. (September), he was criticized for his ineffectiveness.

When McClellan was removed from the command of the Army of the Potomac (Nov. 7, 1862), Burnside (over his own protests) was chosen to replace him. After a crushing defeat at the Battle of Fredericksburg (Fredericksburg, Battle of) (December), Burnside was replaced by General Joseph Hooker (Jan. 26, 1863). Transferred to Ohio, Burnside helped to crush General John Morgan's Ohio raid in July. He then marched into Tennessee, taking Knoxville and holding it against a siege by Confederate troops under General James Longstreet. Returning to the Eastern theatre in 1864, Burnside led his old corps under General Ulysses S. Grant in the Wilderness campaign. In Virginia the fiasco of the “Burnside mine” at Petersburg (Petersburg Campaign)—a mine was exploded under part of the Confederate line, but the assaulting troops were repulsed with heavy losses because of mismanagement—brought about Burnside's resignation. After the war he served as governor of Rhode Island (1866–69) and as U.S. senator from 1875 until his death.