Leaving Sanford the highway runs along the southern side of the Triangle Area, while servicing the smaller towns of Fuquay-Varina and Clayton.

The western terminus of the highway was moved in 1948 to US 15A (Now US 401) in Fuquay-Varina, placing NC 42 on its modern routing south of Raleigh.

NC 42 begins a slow turn to the east south of Hayfield Drive, which it completes before reaching Old Cox Road/Grantville Lane.

East of the intersection, NC 42 makes multiple curves which temporarily adjust its orientation to the northeast and southeast.

NC 42 continues through the unincorporated community before crossing the Deep River and entering into Lee County.

Until reaching Carthage Street the area is mostly residential, however as the road continues east more commercial buildings are found roadside.

The highway passes by East Lee Middle School, along with several warehouses and a mobile home park all before leaving Sanford.

However, as the highway makes a slow turn to the southeast, the houses give way to forests alongside Harris Lake.

NC 42 passes over a railroad operated by Norfolk Southern, briefly before the highway turns directly south.

NC 42 turns to the northeast along Academy Street, and runs adjacent to several fields along with several rural neighborhoods.

By the time the highway intersects Judd Parkway, the fields disappear into a strictly residential area.

Through Cleveland, the route serves as the main commercial district through the rapidly growing suburban area of northern Johnston County.

As the highway continues east, it crosses the Neuse River, another elementary school along with multiple residential developments.

After intersecting Parkwood Boulevard West, most of the stores fade away to a residential section of northwest Wilson.

After intersecting Tilghman Road, the highway takes another right turn toward the southeast, now running along the eastern side of Wilson.

The residential neighborhoods surrounding the road quickly fade to farms and several large factories which are situated on the outside of the town.

[1][4] After passing to the north of the residential community of Larkspur, the highway begins a slow turn to the northeast towards Pinetops.

[1][4] Leaving the center of Pinetops, the highway passes by several more stores and an elementary school before reentering a residential zone on the western side of the town.

Church Street runs through a residential area of the town and crosses a railroad operated by CSX Transportation.

NC 42 meets US 64 Alternate (Canal Street) on the northeastern side of town, before exiting to the east.

The highway makes a general turn to the northeast after intersecting Vine Lane and also enters into a forested area as it approaches US 64.

The highway continues northeast through a mix of small forests and farms, and makes several curves to the north and east.

The highway bypasses the main part of the town to the east, with only a few houses, and several small stores found alongside the road.

Between Lewiston Woodville and Aulander, the highway is relatively straight, making only one turn to the northeast briefly before passing the Luella community.

It meets up with NC 305 at Commerce Street, where several houses are found adjacent to the intersection, however the highway continues through mostly forests and small farms.

Continuing east, the highway runs adjacent to several rural residential neighborhoods west of town.

Memorial Drive continues through predominately residential area, until reaching Catherine Creek Road, where many more small stores are found adjacent to the highway.

As the highway continues to the southeast, the landscape changes back to mostly forests and farmland, however multiple houses are found along the segment between Ahoskie and Powellsville.

After intersecting Commerce Street, NC 42 passes by both the town hall and the post office in Powellsville.

Even after leaving the town limits, the area alongside the highway remains rural residential until reaching Rockpile Road where most of the homes stop.