The highway travels from Goldsboro to Louisburg, connecting various rural communities in between.

In 2008, NC 581 was realigned onto new freeway extension with US 117, removing it from part of Ash Street and overlap with US 13/US 117 Alternate; a year later US 117 would revert to its former route, leaving NC 581 on the new freeway segment.

[4][5] In 2015, NC 581 was rerouted in Bailey, following along the truck route along Main, Benson and Deans Streets; the one block of Sanford Street became SR 1186 and is restricted to all thru trucks with a load limit exceeding 13,000 pounds (5,900 kg).

The justification for the route change was because of the railroad underpass with a 8.6 feet (2.6 m) vertical clearance.

Nine crashes, including a school activity bus, happened between May 1, 2008 and April 30, 2013; also, representatives from Carolina and Northwestern Railroad indicated that they would not allow a widening of the underpass.