The highway serves the Research Triangle area, between Burlington and Raleigh, connecting the cities and towns of Chapel Hill, Durham, Morrisville and Cary.

Turning to the southeast the route runs through some of the outskirts of Burlington before moving through a predominantly rural area.

Approaching Chapel Hill, the highway follows the NC 54 "Bypass" around the town and runs concurrently with US 15/US 501 until reaching Raleigh Road.

The last major change to the routing occurred in 1963 when NC 54 was extended along Hillsborough Street to the then-new US 1 freeway (present day I-440).

After the intersection the road turns more toward the east and runs through an area which is primarily rural with multiple neighborhoods surrounding the route.

NC 54 finishes its eastern turn as it enters another unincorporated community, White Cross.

Multiple strip malls and neighborhoods are located adjacent to the route as it heads southeast towards Durham.

Once reaching Hope Valley Road, a group of stores are found congregated around the intersection.

The route somewhat parallels the freeway and forms the northern border for the Wellington Forest neighborhood.

[1][2] Passing NC 55, the road crosses a railroad track before entering into Research Triangle Park.

At Surles Court, the road makes a shift to turn more toward the east, directly paralleling the railroad NC 54 previously crossed under.

As Chapel Hill Road bears further to the east, the highway splits from the railroad track that it had been previously running alongside of.

Entering into Cary, the road serves as access to the Park West Village Shopping Center and the surrounding apartment complexes.

Continuing further, the road meets back up with the railroad that it had previously broken away from and roughly begins to parallel it again.

Continuing east along Maynard Road, the highway runs along a residential area north of downtown Cary.

NC 54 turns left onto Chapel Hill Road to continue heading east towards Raleigh.

Briefly after the intersection, NC 54 widens to a four-lane divided road and continues that way until reaching Hillsborough Street.

NC 54 provides multiple accesses to the North Carolina State Fairgrounds before intersecting Blue Ridge Road.

Hillsborough Street continues east to access NC State's North Campus and Downtown Raleigh.

[1][2] The routing for the original NC 54 was included on the 1916 map of the planned state highway system in North Carolina.

The road followed along a brief concurrency with NC 703 to the west into Thompsonville, where it then was extended back onto a new routing north to Reidsville.

[18][19] In 2022, an extension to McCrimmon Parkway along the eastern side of NC 54 and the center of town was opened.

NCDOT, the Capital Area Metropolitan Planning Organization, and the Town of Morrisville teamed up on the study of the six-mile (9.7 km) corridor from NC 540 to Maynard Road.

Ideally, the road would become a four- to six-lane superstreet from the Durham County line southeast into Cary.