Burnside was born on May 23, 1824 in Liberty, Indiana, the fourth of nine children of Edghill and Pamela Brown Burnside. Ambrose attended Liberty Seminary as a young boy, but when his mother died in 1841, he was apprenticed to a local tailor. His interest in military affairs and his father's political connections helped him obtain an appointment to the United States Military Academy in 1843. He graduated in 1847, ranking 18th in a class of 38, and was commissioned a brevet second lieutenant in the 2nd U.S. Artillery. He traveled to Veracruz for the Mexican-American War, but arrived after hostilities ceased. He performed mostly garrison duty around Mexico City.
After returning from Mexico, Burnside served two years on the western frontier under Capt. Braxton Bragg in the 3rd U.S. Artillery, a light artillery unit that had been converted to cavalry duty and protected the Western mail routes through Nevada to California. In 1849, he was wounded by an arrow in his neck during a skirmish against Apaches in New Mexico. In 1852, he was appointed to the command of Fort Adams, Newport, Rhode Island, and, while there, he married Mary Richmond Bishop of Providence, Rhode Island, on April 27. The couple had no children.
In 1853, Burnside resigned his commission in the United States Army, and devoted his time and energy to the manufacture of the famous rifle that bears his name, the Burnside carbine. Burnside also became involved in politics, running as a Democrat for one of the U. S. Congressional seats in Rhode Island in 1858. He was defeated in a landslide. The burdens of the campaign and the destruction by fire of his rifle factory contributed to his financial ruin, and he was forced to assign his firearm patents to others. He went west in search of employment and became treasurer of the Illinois Central Railroad, where he worked for, and became friendly with, one of his future commanding officers, George B. McClellan.
At the outbreak of the Civil War, Burnside was a brigadier general in the Rhode Island Militia. He raised a regiment, the 1st Rhode Island Volunteer Infantry, and was appointed its colonel on May 2, 1861. Within a month, he ascended to brigade command in the Department of Northeast Virginia. He commanded the brigade without distinction at the First Battle of Bull Run in July. After his 90-day regiment was mustered out of service, he was promoted to brigadier general of volunteers on August 6, and was assigned to train provisional brigades in the growing Army of the Potomac.
Burnside commanded the North Carolina Expeditionary Force—three brigades assembled in Annapolis, Maryland, which formed the nucleus for his future IX Corps—and the Department of North Carolina, from September 1861 until July 1862. He conducted a successful amphibious campaign from February through May that culminated in Union occupation of over 80% of the North Carolina coast. His success in the battles of Roanoke Island, New Bern, and Fort Macon, the first significant Union victories in the Eastern Theater, earned him promotion to major general on March 18. In July, his forces were transported north to Newport News, Virginia and became the IX Corps of the Army of the Potomac.
Burnside commanded the I Corps and IX Corps at South Mountain, Maryland and the IX Corps at Antietam, after declining command of the Army of the Potomac twice. Burnside was aware of his deficiencies as a commander and did not want the responsibility. However, he was assigned to command the Army of the Potomac by Pres. Abraham Lincoln on November 7, 1862. The command did not last long, as Burnside was replaced in January 1863, after the Union failure at Fredericksburg, Virginia the previous month.
Burnside bounced around for the remainder of the war, first commanding the Department of the Ohio in east Tennessee. In May 1864, he brought his old IX Corps back east and participated in the Overland Campaign, and the battles of The Wilderness and Spotsylvania Courthouse. Burnside and his subordinates were blamed for the Union debacle at the Battle of the Crater near Petersburg, Virginia on July 30, 1864. Burnside was placed on leave on August 14, and he finally resigned his commission on April 15, 1865.
Following the war, Burnside worked for a number of railroad companies and resumed his political career. He was governor of Rhode Island from 1866 to 1869 and U.S. Senator from 1874 until his death on September 13, 1881. He also served as Commander-in-Chief of the Grand Army of the Republic, a Union veterans organization, from 1871 to 1872. He was the first president of the National Rifle Association when it was founded in 1870.