 In 1969, the business route, now joined with the East St. Louis business route was redesignated US 66, while Bypass US 66 was redesignated Interstate 270.

Business US 66 in the St. Louis, Missouri area was actually one of two business routes in the entire metro St. Louis area.A separate Business US 66 existed in the East St. Louis, Illinois area.In 1939, US 66 was routed over the Chain of Rocks Bridge to have the route bypass the city.