He was one of 15 children and youngest son of Major John Whistler, Commandant of Fort Wayne, and his wife Anna Bishop. His first marriage was to Mary R. Swift (d. 1827), with whom he had three children: George William (1822-1869), Deborah Delano (1825-1908) and Joseph Swift (1824-1840).
His second wife was Anna Matilda McNeill, with whom he had five sons: James Abbott (1834-1903), William McNeill (1836-1900), Kirk Boott (1838-1842), Charles Donald (1841-1843), and John Bouttatz (1845-1846).
He graduated from the USMA, West Point, NY in July 1819 with the rank of Second Lieutenant in the Corps of Artillery. He served at a topographer in 1819-21. He became Assistant Professor of Drawing at West Point 1821-22. From 1822 to 1828 he was attached to the Commission tracing the international boundary between Lake Superior and Lake of the Woods. In 1828 he worked for the Baltimore and Ohio Railroad, which sent him to England to study railroads and steam locomotive construction. In 1829 he was promoted to 1st Lieutenant, and in 1830 he co-surveyed with William Gibbs McNeill the construction of the Baltimore and Susquehanna Railroad. In 1831 they supervised the construction of the Stonington Railroad. Whistler resigned from the army in 1833.
He became superintendent of the Locks and Canals machine shop from 1834 to 1837 and was engaged in the design of the earliest locomotive built in New England. Whistler copied Stephenson's Planet locomotives but appears to have introduced no original concepts to the design of railway engines. Several years later he recognized the need for heavier locomotives, but unfortunately he chose Ross Winan's unsuccessful 0-8-8 Crabs to meet his need. In 1837 he and McNeill surveyed the Nashua-Concord (New Hampshire) portion of the Concord Railroad. Between the 1830s and 1842, he was also involved in the building of the Western Railroad (Boston-Worcester-Springfield-Greenbush, New York).
In 1842 he went to St Petersburg, Russia, to supervise the construction of the Moscow to St Petersburg Railway but died of cholera two years before its completion, on 7 April 1849.
Evelyn Jasiulko-Harden, 'Major George Washington Whistler, Railroad Engineer in Russia: 1842-49,' Ex Oriente Lux, Mélanges, vol. 1, Brussels, 1991, p. 148; Albert Parry, Whistler's Father, Indianapolis, 1939; John H. White, A History of the American Locomotive, Its development, 1830-1880, New York, 1968, p. 457.