On the outbreak of the American Civil War Canby was appointed commander of the Department of New Mexico and successfully prevented an invasion of California by Henry Sibley.
Canby went to Washington as an assistant adjutant general and commanded troops in New York City. Appointed commander of the Military Division of Western Mississippi, he captured Mobile, Alabama, and forced the surrender of Edmund Kirby-Smith.
Edward Richard Canby, promoted to the rank of major general, remained in the army but on 11th April, 1873, while commander of the Department of Columbia, was murdered in Siskiyou, California by Modoc led by Kintpuash during negotiations over a peace treaty.
General Canby was an officer of great merit. He was naturally studious, and inclined to the law. There have been in the army but very few, if any, officers who took as much interest in reading and digesting every act of Congress and every regulation for the government of the army as he. His knowledge gained in this way made him a most valuable staff officer. He was an exceedingly modest officer, though of great talent and learning.