The Grand Trunk Western Railroad, a US subsidiary of the Canadian National Railway had a fleet of 43 4-8-4s. The GTW bought 12 Class U-3-a "Confederations" (as the 4-8-4s were called by CNR) from the American Locomotive Company in 1927 and was one of the first railroads to use them. These locomotive were assigned road numbers 6300 through 6311. They had 73" drivers, 26.5 x 30 cylinders, a boiler pressure of 250 psi, a tractive effort of 60,000 lbs and weighed 399,000 pounds.

Another six 4-8-4s were bought in 1938 from the Lima Locomotive Works and designated Class U-4-b and assigned road numbers 6405 through 6410. These locomotives had 77" drivers, 24 x 30 cylinders, a boiler pressure of 275 psi, a tractive effort of 52,500 lbs and each weighed 382,700 pounds.

In 1942 and 1943, the GTW bought another 25 "Confederations" from ALCO. These locomotives were designated Class U-3-b and had 73" drivers, 26 x 30 cylinders, a boiler pressure of 250 psi, a tractive effort of 59,000 lbs and weighed 403,000 pounds. They were assigned road numbers 6312 through 6336.

On March 23, 1960, GTW locomotives numbers 6319 and 6322 had the distinction of hauling the last regularly scheduled main line steam powered passenger train in the United States. Number 6319 led the 15 cars of the first section of Train #21 from Detroit to Durand, MI while number 6322 led the 22 cars of the second section.

There are two surviving GTW "Confederations"; number 6323 at the Illinois Railway Museum in Union, IL and number 6325 at the Ohio Central Railroad in West Lafayette, OH.