He was born in Portland, Maine into a seafaring family; his father was sea captain Enoch Preble, whose brother was the noted Commodore Edward Preble. George entered the Navy as a midshipman on 10 December 1835, serving on the United States until 1838.
He was in the Florida war in 1841, and was on the St. Louis for its circumnavigation of the world in 1843-1845, taking ashore the first American force to land in China. In the Mexican-American War, he participated in the capture of Alvarado, Veracruz, and Tuxpan. He became master 15 July 1847, and lieutenant 5 February 1848. While serving on the frigate St. Lawrence, he went with Matthew C. Perry to Japan in 1853, during which Preble surveyed various harbors in the Far East.
After a period as lighthouse inspector and at Charlestown Navy Yard, he served on the Narragansett, 1859-1861, then took command of the gunboat Katahdin, serving with David Farragut on the Mississippi River, and was promoted to commander 16 July 1862.
When the Confederate cruiser CSS Florida eluded him, Preble was dismissed from the Navy, but reinstated after the captain of the Florida testified that superior speed alone had saved him. Preble then commanded the St. Louis, only to have the Florida escape him once again, off Madeira.
After the war, Preble commanded the USS State of Georgia, and rescued 600 passengers from the wrecked steamer Golden Rule. He was at the Boston Navy Yard from 1865 to 1868, where he was promoted to Captain (16 March 1867), then commanded the Pensacola until 1870. He became Commodore on 2 November 1871, commanded the Philadelphia Navy Yard from 1873 to 1875, became Rear Admiral on 30 September 1876 and retired in 1878.
In the meantime, Preble had become known as a writer on naval and historical topics, and as a collector of naval documents. He was also active in various learned and genealogical societies of the time. In 1868, he published a genealogical history of the Preble family in America (linked below), which included his biography and portrait, (pp. 200-232), as well as that of his famous uncle, Edward The book also set forth a defense of his actions that led to his dismissal from the Navy, as well as the efforts of himself and others that led to his exoneration and reinstatement. In 1872, he published his History of the American Flag, which is still cited as a source. He also took care of the original "Star-Spangled Banner" which had flown over Fort Henry, and had the flag sewn to a piece of sailcloth in order to preserve it.