McDowell Co.: Marion; runs along North Fork of Catawba River. Ascends the Blue Ridge between Honeycutt Mountain (to the west) and Linville Mountain (to the east). Elevation ranges from about 1300 feet at Marion to over 3600 feet near the southernmost junction with N.C. 194. 
Although two runaway truck ramps have been built for southbound traffic, the climb is not as severe or as twisty as what can be found on most other routes up the Blue Ridge. This fact is not lost on "Floridiots" in their campers and Town Cars, about whom James Kilbourne writes: "The trip from Marion to Boone takes 20 minutes longer in the summer than in the winter because of the silver-haired warriors." (All the more reason to recycle the Berlin Wall for use at Florida's northern border.) 

Avery Co.: BRP milepost 318; Linville Falls; Pineola; Linville. Provides access to Grandfather Mountain (map). BRP milepost 306. Ascends to about 4400 feet at the entrance to the Grandfather Mountain toll road. 

Watauga Co.: Blowing Rock; Boone; BRP milepost 294. 

Ashe Co.: Jefferson; crosses New River

U.S. 221 was born in 1930. At first, it existed only in North Carolina and ran from U.S. 19E in Ingalls to U.S. 21 near Sparta.  221 was first signed over the entire length of that era's N.C. 691. That's deceiving, though, because 691 was numbered as a slew of different things before 1930: N.C. 176, 175, 17, 60 and 69, in addition to an unnumbered stretch or two. On the other hand, 221's multiplexes with N.C. 181 and N.C. 194 have not changed since 221's birth. See Map #1.  To reiterate, 221's southern terminus was originally at U.S. 19E, but it doesn't touch 19-anything today. The original 221 between the Linville Falls area and U.S. 21 survives to this day without any major reroutings, with one noteworthy exception, which is discussed below.

1. 1931 Gousha map

221's Extension  In late 1931 or early 1932, 221 was extended northward into Virginia along U.S. 21/N.C. 26. Also, it was extended into South Carolina over what had been:  N.C. 207, from the S.C. line through Cliffside, Henrietta and Caroleen to Forest City. Map #2 shows this alignment. This road is now U.S. 221A. U.S. 74/N.C. 20, from Forest City to Rutherfordton N.C. 19, from Rutherfordton north through Marion to U.S. 19E, and N.C. 69, from 19E's junction with today's N.C. 226 up the Blue Ridge to the already-existing 221 at Altamont.

2. 1940 RMcN map

In early 1933, 221 was taken off the old N.C. 19 to Spruce Pine, and followed the North Fork of the Catawba River up the Blue Ridge to Linville Falls instead. No longer would 221 touch U.S. 19E. This was part of the great renumbering; the road along the Catawba River had been part of N.C. 28. 
Immediately south of its ascent up the Blue Ridge, 221 once ran slightly east of its current alignment. The older road, which spends most of its length east of the Catawba, is now varyingly called Old Linville Road or Old U.S. 221. There's also a rather lengthy Old U.S. 221 south of Marion. No idea when either of these roads were bypassed. 
 

In the early 1940s, the original 221 between Chesnee, S.C. and Rutherfordton was bypassed to the west, partially over what had been N.C. 741. Map #3 at right shows the bypass to be under construction. The road probably opened by 1942, at which point the original 221 south of Rutherfordton was re-signed as U.S. 221A.  In 1952 or early '53, U.S. 221 was rerouted north of Boone. Since 1930 it had run due north from Boone over today's N.C. 194. That year, it was sent east over U.S. 421 to Deep Gap (near the ECD) and then north over a previously unnumbered road to meet up with the older 221, which became an extension of 194. While this newer alignment is a mile or two longer than the older one, it's much less twisty.

3. 1941 G. Drafting map

In the mid-1980s, 221/321 was widened to four lanes between Blowing Rock and Boone. Also, a new four-lane 221 around the south of Boone was built. The original 221/321 ran into the center of Boone; after 221 was sent around the south of town the old route was designated as 321 only. 

The four-lane 221 in McDowell County was first built as a new western bypass of Marion in 1992. By 1997, 221 north of Marion was widened to four lanes as far as 221's separation from N.C. 226. The Marion bypass is signed as 221/226, whereas the old 221/226 through Marion is now signed only as Business 221.

U.S. 221, 321 and 421 all go through part of Boone, and before the mid-1980s, all three routes met in the center of town. (Nowadays, each pair of two highways meets or is multiplexed somewhere in Boone.) Boone is one of the few settlements in the country which contains three U.S. highways from the same "family", and the only place in the U. S. of A. which contains three three-digit U.S. highways from the same parent. The map at the top of the page illustrates this phenomenon. 

U.S. 221 was named as one of Car and Driver's Ten Best Roads in its January 1990 issue. It probably received that honor due to two particularly twisty stretches: the stretch near Grandfather Maountain, between Linville and Blowing Rock, and the stretch between Jefferson and U.S. 21 near the Virginia line. While these two parts of 221 are decidedly unstraight, they have quite different personalities: 

Sign the bypass around Marion as U.S. 221 only, and sign the original 221 through town as N.C. 226 only. Business designations shouldn't be used where another number is handy. 

Barring that last sentence, sign a Business 221 through the center of Boone, so that 221, 321 and 421 can once again meet.