Known as The Sunset Highway in Spokane, U.S. 10 was the first major highway across the Northern United States. It was commissioned in 1926. At its first opening, U.S. 10 ran from Seattle to Detroit with a ferry carrying it across Lake Michigan from Manitowoc, Wisconsin to Ludington, Michigan.

Interstate 90 replaced The Sunset Highway as the major west-east course from Seattle through Spokane and on to the Washington border. Exits are numbered as mileposts which start at 1 in Seattle and finish at 296, just before Idaho.

U.S. 2 is routed along the old Sunset Trail. It used to be known as the Alternate U.S. 10. It is roughly parallel and just north of I-90, and runs from Grand Coulee to Spokane. Farther north, State Road 20 is tougher to drive, but offers a scenic route through farm, timber and mining country.

S.R. 195 will take you south of Spokane along Latah Creek (formerly Hangman Creek), past the bottom of the South Hill of Spokane, or farther south to Rosalia, Colfax, and Pullman.

U.S. 395 runs from Spokane to the Canadian border as the major north axis.