Interstate 64 (I-64) is an Interstate Highway in the Midwestern and Southeastern United States. Its western terminus is at I-70, U.S. 40, and U.S. 61 in Wentzville, Missouri. Its eastern terminus is at an interchange with I-264 and I-664 at Bowers Hill in Chesapeake, Virginia.

The Missouri Department of Transportation has completed extending I-64 to I-70 in Wentzville, Missouri. In April 2007, construction started to rebuild 10.5 miles (16.9 km) of I-64 in St. Louis, Missouri, from Spoede Rd. to Kingshighway. This project included repaving the entire road, rebuilding the overpasses and interchanges, adding a fourth lane between Spoede Rd. and I-170, and connecting I-64 to I-170 in all directions. Construction resulted in the complete closure of portions of the expressway in 2008 and 2009. In 2008, I-64 was closed from I-270 to I-170, re-opening December 15, 2008. Beginning December 15, 2008, I-64 from I-170 to Kingshighway Blvd. was closed. On December 7, 2009, Interstate 64 was complete in its entire length in Missouri from the Poplar Street Bridge to I-70 in Wentzville.