PA 110 begins at an intersection with PA 954 in the borough of Creekside, heading southeast on two-lane undivided Indiana Road past homes.

The road passes under Norfolk Southern's Shelocta Running Track railroad line before continuing into Washington Township, where it crosses a Buffalo and Pittsburgh Railroad line at-grade.

PA 110 continues into Rayne Township before entering the borough of Ernest, where the road becomes Main Street and passes residences.

After leaving Ernest for Rayne Township again, the route heads east away from the creek and railroad and runs through forested areas with a few homes and small farms as an unnamed road.

The route heads through rural areas of residences before reaching its terminus at a trumpet interchange with US 119.