Edward R.S. Canby was born on November 9, 1817 at Piatt's Landing, Kentucky. He attended Wabash College before transferring to the U.S. Military Academy at West Point. He graduated in 1839 and was appointed second lieutenant of the 2nd US Infantry. On August 1, 1839 he married Louisa Hawkins of Indiana.
Canby served in the Second Seminole War and the Mexican War, receiving three brevet promotions up to lieutenant colonel. From 1849 to 1851 he was posted to the Adjutant General's Office in California and, because of his knowledge of the Spanish language, served as Custodian of the California Archives from 1850 to 1851. He commanded the Utah Territory during the Utah War of 1857-58 and conducted a campaign against the Navajo tribe in New Mexico as the commander of Fort Defiance in 1860.
On May 14, 1861, Canby was promoted to colonel of the 19th US Infantry. In February 1862, his forces were defeated at the Battle of Valverde by Confederate forces under the command of Brig. Gen. Henry Hopkins Sibley, with whom Canby had served during his time in the Utah and New Mexico territories. However, only a month later, in March 1862, Canby's forces were victorious at the Battle of Glorieta Pass, and Canby was promoted to brigadier general.
After a time on administrative duty, Canby was assigned commanding general of the city and harbor of New York, a position he held from July through November of 1863. In November 1863, he was assigned to the Office of the Secretary of War in Washington D.C. In May 1864, Canby was promoted to major general and took command of the Military Division of Western Mississippi. He was wounded by a sharpshooter while aboard the USS Cricket on the White River in Arkansas on November 8, 1864.
Canby commanded Union forces in the Mobile Campaign in the spring of 1865, culminating in the Battle of Fort Blakely in April. He accepted the surrender of troops under Confederate generals Richard Taylor on May 4, 1865 and Edmund Kirby Smith on May 26, 1865. He was considered an excellent administrator, but many questioned his abilities as a field commander.
Throughout the Reconstruction period, Canby commanded numerous departments, including the 2nd Military District, which included North Carolina, from August 1867 to August 1868. North Carolina governor Jonathan Worth considered him to be sincere and honest. Canby was awarded an honorary Doctor of Laws degree from Wesleyan University in Connecticut on July 21, 1870, only one month before being posted to command the Pacific Northwest. He was in command of the territory when the Modoc War broke out in 1872. During peace negotiations on April 11, 1873, the Modoc leaders killed Canby and other members of the peace delegation. Canby was the only U.S. general killed during the Indian Wars. He was buried in Crown Hill Cemetery in Indianapolis, Indiana on May 23, 1873.