Interstate 66 (I-66) is an Interstate Highway in the eastern United States. As indicated by its even route number, it runs in an east–west direction. Its western terminus is in Middletown, Virginia, at an interchange with Interstate 81; its eastern terminus is in Washington, D.C., at an interchange with U.S. Route 29. Interstate 66 has no physical or historical connection to U.S. Route 66.

The E Street Expressway is a spur from Interstate 66 into the Foggy Bottom neighborhood of Washington, D.C.

Because I-66 is the only Interstate Highway running west from Washington, D.C., into Northern Virginia, traffic on the road is often extremely heavy. For decades, there has been talk of widening I-66 from 2 to 3 lanes each way inside the Capital Beltway (Interstate 495) through Arlington, Virginia, although many Arlington residents are adamantly opposed to this plan.

In 2005, the Virginia Department of Transportation (VDOT) studied the prospect of implementing a one-lane-plus-shoulder extension on westbound I-66 within the Beltway (in an attempt to reduce congestion for people commuting away from D.C.).