IL 64 then travels east through Mount Carroll, Lanark, Mount Morris, Oregon, Sycamore, Lily Lake, Saint Charles and the western suburbs of Chicago before terminating at U.S. Route 41 (US 41, Lake Shore Drive) on the city's north side.

At St. Charles, IL 64 enters the Chicago metro area and becomes a four-lane road, taking on the name of Main Street.

Just east of St. Charles, IL 64 becomes North Avenue and retains this designation until just before its terminus in Chicago at US 41 (Lake Shore Drive).

From Elmhurst to Interstate 294 (I-294) it remains a four-lane surface street, but it widens to a six-lane divided highway once again through the towns of Stone Park and Northlake.

One-half mile (0.8 km) west of US 41, IL 64 turns north onto LaSalle Boulevard, and then east, before terminating at Lake Shore Drive.

For a time, Illinois House of Representatives minority leader Lee Daniels supported a plan to reduce North Avenue from four lanes to two, prohibiting trucks from traveling through the residential neighborhood.