For the bulk of its length, it runs parallel to Interstate 64 and approximately 10 miles (16 km) north of it.

Traffic conditions on the stretch between Princeton and Mount Carmel are notorious for often being congested with a large number of coal trucks between local mines and Gibson Generating Station, located near the route's western terminus and Illinois resident employees of both the plant and Toyota Motor Manufacturing Indiana and suppliers in Princeton using the same two lane road in their commute combined with decreases in local grocery stores resulting in more senior citizens on the main roads often result in severe traffic congestion during two distinct periods in the day.

Due to the coal truck traffic from Gibson County Coal's new mine near Owensville, the Indiana 64-65 CR 650 Intersection, located halfway between Princeton and Mount Carmel, received a long-awaited upgrade from flashing lights to a full traffic light intersection in December 2014, allowing a more orderly traffic flow and reducing the amount of fatal crashes at the junction.

The Gibson County Sheriff department and Indiana State Police seldom patrol this stretch of deadly highway.

Despite INDOT continuing to insist there is no need, many commuters in both Indiana and Illinois have been pushing for widening it to 4 lanes, in part or in whole from Princeton to Mount Carmel.