It connects the cities of Rock Hill, York, and Kings Mountain, North Carolina.

SC 161 is a multi-lane highway, traversing from U.S. Route 21 (US 21) and Interstate 77 (I-77), through the northern part of Rock Hill and north around York, to the back entrance area of Kings Mountain State Park and Kings Mountain National Military Park, and ends at the North Carolina state line.

In 1959, SC 161 was extended south, through York, to its current southern terminus at US 21 in Rock Hill.

After an intersection with the western terminus of SC 324 (McFarland Road), they curve to the northwest and then enter the main part of the city.

Just after they pass the York Public Library, they intersect Roosevelt Street, which leads to the chamber of commerce.

The two highways travel through rural areas of the city until they intersect the northern terminus of US 321 Bus.