Past Bloomsburg, the route continues north through Millville and runs through the eastern part of Lycoming County.

PA 42 heads into Sullivan County and runs concurrent with US 220 between Beech Glen and Muncy Valley before it loops west through Eagles Mere and reaches its terminus in Laporte.

The route turns east and crosses into Conyngham Township, becoming South Main Street and heading into forested areas.

PA 42 widens to a four-lane road and heads to the northwest, passing through the residential community of Aristes, where it narrows back to two lanes.

[2][3] The road curves to the northeast and becomes Numidia Drive, heading into the Weiser State Forest and turning to the northwest as it crosses Big Mountain.

Continuing to the west-northwest, PA 42 enters Locust Township as it crosses Little Mountain, leaving the state forest and turning to the north.

PA 42 curves to the northwest as it heads through more rural areas, crossing the Roaring Creek and continuing into Catawissa Township.

PA 42 runs through wooded areas immediately to the west of the railroad tracks with the Susquehanna River a short distance to the east.

[2][3] At this point, PA 42 heads northeast concurrent with US 11 on four-lane divided Montour Boulevard, crossing the Fishing Creek into the town of Bloomsburg.

Immediately after, the route splits from US 11 at another interchange to the west of the Bloomsburg Fair fairgrounds, heading northwest on four-lane divided Mall Boulevard and crossing the Fishing Creek back into Montour Township.

PA 42 heads through wooded areas with some nearby commercial development, turning to the north and passing near some farmland, widening back into a four-lane divided highway.

PA 42 heads back to the north and continues through more rural areas, crossing into Madison Township and turning to the west near Mordansville, becoming an unnamed road.

The road turns back to the north and heads through farmland with some homes, crossing the Little Fishing Creek into Mount Pleasant Township.

The route curves to the northwest and runs through more wooded areas with some farms and residences to the northeast of the creek, entering Greenwood Township and turning to the north, passing through the residential community of Eyers Grove.

Here, the road again runs along the east bank of the Little Fishing Creek as it becomes an unnamed and heads through rural areas of residential and commercial development, passing through Iola.

The road heads into more forested areas with a few homes and passes west of the community of Unityville, turning northwest and intersecting PA 118.

PA 42 continues through agricultural areas and heads into Franklin Township, turning to the northwest and passing through more farmland and woodland with a few residences.

[2][4] PA 42 heads into Davidson Township in Sullivan County, turning to the north and passing through wooded areas with some fields and homes.

At this point, the route turns north to form a concurrency with US 220 on the Appalachian Throughway, heading through a mix of farmland and woodland with a few residences.

[7] With the creation of the U.S. Highway System in 1926, the road between Reading and Centralia was designated as part of US 120, a route that ran from Philadelphia northwest to Erie, while the road between Laporte and South Waverly was designated as part of US 711, a route that ran from Northumberland north to South Waverly.