The northern terminus is at U.S. Route 22 (US 22) near the East Hanover Township hamlet of Grantville though some signage has it continue north past Interstate 81 (I-81) to PA 443.

The route runs north through Lancaster County, passing through Maytown before reaching Elizabethtown.

The road heads northeast and enters the borough of Elizabethtown, coming to a bridge over Amtrak's Keystone Corridor railroad line.

At this point, the route becomes concurrent with PA 341 Truck in the northbound direction and heads into areas of farms and woods as a two-lane undivided road, crossing the Conewago Recreation Trail.

Past this intersection, PA 743 passes through more rural areas with some homes and businesses, continuing into Derry Township and becoming Fishburn Road.

The route turns northwest and passes residential neighborhoods as it enters the community of Hershey.

PA 743 turns north onto Cocoa Avenue and passes between businesses to the west and farms to the east as it reaches the US 322 intersection.

The road comes to a bridge over Norfolk Southern's Harrisburg Line before it runs between the Hersheypark amusement park to the west and ZooAmerica to the east.

After this interchange, the route turns north into rural areas and passes a short distance to the west of Hollywood Casino at Penn National Race Course.

Bow Creek Road comes to its northern terminus at an intersection with PA 443 at the base of Blue Mountain.

[9][10] In the 1940s, the northern terminus of PA 743 was cut back to its current location follow a realignment of US 22 from Jonestown Road to Allentown Boulevard.

[13] In 2010, a $12 million project began to realign PA 743 at its intersection with US 422 in Hershey, eliminating a short concurrency.

The route follows Fishburn Avenue connecting US 322 with southbound PA 743, allowing trucks to avoid downtown Hershey.