U.S. Route 101, or U.S. Highway 101, is an important north–south U.S. highway that runs through the states of California, Oregon, and Washington, on the West Coast of the United States. It is also known as El Camino Real (The Royal Road) where its route along the southern and central California coast approximates the old trail which linked the Spanish missions, pueblos, and presidios. It merges at some points with California Highway 1.

Though U.S. Route 101 remains a major coastal north–south link along the Pacific coast north of San Francisco, it has been replaced in overall importance for transport through the West Coast states by Interstate 5, which is more modern in its physical design, goes through more major cities, and has more direct routing due to significantly easier geography over much of the route. Route 101 is a major parallel freeway or highway between Los Angeles and San Francisco, and is an alternative to the Interstate for most of its length. In 1964, California truncated its southern terminus in Los Angeles, as Interstate 5 replaced it. The old road is known as county road S-21 or Historic Route 101 in northern San Diego County.

The nearly 2,500 km (1,550 mi)-long highway's "northern" terminus is in Tumwater, Washington: the route remains along the Olympic Peninsula's coastal perimeter west, north, and east; the northernmost point on the highway is in Port Angeles. The southern terminus of U.S. 101 is in Los Angeles at the East Los Angeles Interchange, the world's busiest freeway interchange.