U.S. Route 101, or U.S. Highway 101, is a U.S. highway running north-south through the states of California, Oregon, and Washington, on the far 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 State Route 1.

According to the AASHTO numbering scheme for U.S. Highways, three-digit route numbers are generally subsidiaries of two-digit routes. U.S. 101 is treated as a primary, two-digit route with a first digit of ten, not a spur of U.S. 1. Thus U.S. Route 101, not U.S. 99, is the westernmost north-south route in the U.S. Highway system.

U.S. Route 101 was once the major north-south link along the Pacific coast. It has been replaced in importance by the highways of the Interstate Highway System, specifically Interstate 5, which is more modern in its physical design. Route 101 is still in use as a highly traveled alternative to the Interstate for most of its length. A notable exception is where the alignment is shared with that of I-5 and the route number U.S. Route 101 has been changed to I-5, beginning about one mile (1.6 km) east of downtown Los Angeles and continuing south to San Diego.

The highway's "northern" terminus is in Olympia, Washington; though the northernmost point on the highway is roughly around Port Angeles. The southern terminus of U.S. 101 is in Los Angeles, California at the East Los Angeles Interchange, the world's busiest freeway interchange.