The nearest major north–south highway, Interstate 39, runs parallel to Illinois 29, but approximately fifty miles to the east.

Starting at U.S. 6/Illinois 89 at the north edge of Spring Valley, the road passes through the small towns of Putnam and Henry, intersecting Illinois Route 18 at Henry.

It then runs beneath the bluff at Hopewell before becoming 4th Street, the main north–south artery through Chillicothe.

In East Peoria, Route 29 splits from Interstate 74 and proceeds south, entering Creve Coeur on Main Street and providing an interchange with Interstate 474.

Route 29 enters Springfield at the Abraham Lincoln Capital Airport, and runs around the north and east sides of the city.