North Carolina Highway 281 is a primary state highway in the state of North Carolina. The highway runs north–south, connecting communities in western Jackson County and scenic areas of southwest Transylvania County. It is the only North Carolina state highway that changes numbers when crossing into South Carolina.

NC 281 is a 36.6-mile (58.9 km) two-lane mountain highway that begins at the South Carolina state line in Jackson County, before quickly entering Transylvania County. It overlaps with US 64 near Sapphire, then goes 2.5 miles (4.0 km) east where it splits and continues north to Lake Toxaway. Continuing northwest, the highway becomes aggressively curvy, steep and narrow (with some locations with no road markings or lines). NC 281 crosses back into Jackson County at Owens Gap (3,590 ft (1,090 m), highest point on route), near Round Mountain to the northeast. The road widens again near the Tuckasegee River and passes by several lakes before ending in Tuckasegee.

The overall route shows the very best of what the Nantahala National Forest has to offer, but it is not recommended for commercial trucks, recreational vehicles or buses. In the winter, the highway can be considerably dangerous in snow and ice, and should not be attempted without proper equipment.

Whitewater Way is an 9-mile (14 km) byway from near Sapphire to the South Carolina state line. It is named after the Whitewater Falls, which at 411 ft (125 m), are the highest east the of the Rockies. Various other falls can also be found along Horse Pasture River and multiple trails connect the area with rare shortia found in the area. The byway is not recommended for recreational vehicles or buses.

Established in 1930 as a new primary route, it went from Lake Toxaway to Tuckasegee. Around 1982, NC 281 was extended southwest (overlapping US 64) onto secondary roads to connect travelers to the Whitewater Falls area. SC 130 was extended to the state line in 1987, creating the only non-continues highway number connection between the North and South Carolina.