U.S. Route 99 was the main north-south highway on the West Coast of the United States until 1964, running from Calexico, California, on the U.S.-Mexico border to Blaine, Washington, on the U.S.-Canada border. It was a route of the United States Numbered Highways, assigned in 1926 and existing until it was replaced for the most part by Interstate 5. Known also as the "Golden State Highway" and "The Main Street of California," US 99 was an important route in California throughout much of the 1930s as a route for Dust Bowl immigrant farm workers to traverse the state. Large portions are now California's State Route 99, Oregon Route 99, and Washington's State Route 99.

The highway connected to British Columbia Highway 99 at the Canadian border.