From a question in the September 13th Wilmington (NC) Star News "Where does US-421 begin and end?"
It begins in Michigan City, Indiana, and ends at Fort Fisher, North Carolina south of Kure Beach (about twenty miles south of Wilmington. Along the way, the highway passes through Kentucky, Tennessee and Virginia as well.
When the road was first built in the 1930s, it began in Boone, NC and had an eastern terminus in Greensboro, NC, according to website USends.com.
By the mid-1930s, the highway had been expanded to Cumberland Gap, Virginia. After the completion of the Cumberland Gap Tunnel, the northern terminus of US-421 was relocated in 1950 to forty miles east of Bristol, Tennessee.
Then, northern terminus was Bedford, Kentucky in the early 50s and then to Michigan City.
I Have "Clinched" This One. --RoadDog