NC 561 is a 101-mile (163 km) North Carolina state highway and a rural traffic artery connecting Louisburg and Ahoskie with many small-to-medium sized towns in the "Down East" and Coastal Plain regions within minutes from the Virginia state line. NC 561 is a spur of NC 56, although the two highways never actually intersect.

The eastern terminus of NC 561 begins at NC 45 in Harrellsville and proceeds west to Ahoskie where it meets with US 13 and NC 42 just outside of town. All three are concurrent (Memorial Drive) upon entering Ahoskie until reaching Academy Street. From there, NC 42 turns left and the other two highways turn right...bypassing downtown Ahoskie to the west. NC 561 will turn left onto West 1st Street, continuing westward towards Rich Square. There are two junctions along the way (NC 11 and NC 461) before merging with NC 305 near the Hertford/Northampton County line. The two highways run concurrent into Rich Square, passing NC 35 to junction with US 258. As NC 305 continues straight towards Jackson, NC 561 turns left and joins US 258 at it passes through Rich Square heading south towards Scotland Neck.

The two highways pass NC 308 south of Rich Square on its way into Halifax County, where NC 561 turns right and proceeds towards Halifax...meeting NC 481 in Tillery. NC 561 will turn right onto US 301, NC 903 and NC 125 just south of Halifax and then turn left a short ways up and continue west towards Brinkleyville. The highway will make a right at Beaver Dam, just before its junction with I-95 (Exit #160 off the interstate). NC 561 will meet NC 4 and NC 48 at Brinkleyville, where NC 4 will run concurrent with NC 561 past Medoc Mountain State Park. The highway will eventually break off heading north to Littleton as NC 561 continues west to Hollister. NC 43 will join the highway past Hollister for a short distance before NC 561 breaks off and travels to Centerville, crossing NC 58 in town. NC 561 will continue southwest into Louisburg where it meets its western terminus at US 401 and NC 39, just a little ways north of NC 56.

NC 561 has nine highway concurrencies along its route. These include...

NC 561 was formed in 1925 and initially ran northeast from NC 56 in downtown Louisburg (East Nash & Main Streets) to NC 58 in Centerville. It was extended in 1928 to US 17-1 and NC 40 in Halifax, now highways US 301, NC 903 and NC 125. The highway was extended further in 1931 to US 258 and NC 12 near Spring Hill (now just US 258). Between 1954 and 1963, NC 561 was extended once again along US 258 to Rich Square and then eastward out through Ahoskie to its current eastern terminus at NC 45 in Harrellsville. During this time, its western terminus was moved over to the new Louisburg Bypass (US 401 and NC 39).