Montgomery Co.: EXITS for Candor, Biscoe, and Star 

Randolph Co.: EXITS for Seagrove and North Carolina Zoological Park (via NC 159), Asheboro, and EXITS for Randleman, Level Cross; Asheboro 

Guilford Co.:Greensboro (Henry Blvd, Wendover Av, Battleground Av); Guilford Courthouse Nat'l Military Park; Summerfield

Rockingham Co.:Madison, Mayodan, Stoneville

US 220 was an original 1927 US Route, but did not reach North Carolina until 1935 when it was extended south from Cumberland, MD. US 220 replaced: US 311-NC 77 from Virginia to Madison; US 411-NC 704 from Madison to Greensboro, US 411-NC 70 Greensboro to Candor; US 411-NC 170 Candor to Norman; US 15-NC 75 from Norman to Rockingham.
More specifically, US 220 followed today's Price Rd from the Virginia line down to today's US 220 Business for Stoneville, Mayodan, and Madison. Then US 220 followed today's US 220 to NC 68, which it followed to Sylvania Rd. It then jogged east on US 158 (current NC 65) then south on Parrar Store Rd before rejoining today's US 220 through Summerfield (possibly using Summerfield Rd). Approaching Greensboro, US 220 followed Battleground Rd (runs east of today's Battleground Ave) down to Wendover Ave, then east to N. Elm St, then cutover to Greene St via Price St. From there it jogged east on Edwards Pl and Asheboro St before heading due south out of Greensboro on S. Elm St. US 220 then cut west on a street (can't tell but probably north of today's I-40/85 Bus) to Randleman Rd, which it followed all the way to Level Cross (It does not appear that Old Randleman Rd was ever US 220, though it appears to have been NC 70 in 1925).

From Level Cross US 220 followed today's US 220 Business through Randleman and Asheboro, then Ulah. US 220 continued south on today's US 220-A to Seagrove. US 220 then veered east on today's NC 705 for a mile, then headed south again on today's "Old US 220", where it passed through a tiny corner of Moore County before meeting back up with today's 220-A in Asbury. US 220 continued south on 220-A through Star, Biscoe, and Candor before using today's US 220 through Ellerbe to approach Rockingham. US 220's original south end was at US 74 in Five Points, using Ellerbe Rd.

By 1939, US 220 was given the more direct route south of Seagrove using today's US 220-A to Asbury. The old route became part of a longer NC 705 and "Old US 220".  

Between 1947-50, it appears US 220 changed its Greensboro Routing to use Battleground Ave then US 220 split its routing (but not onto oneway streets, I don't believe). SB used the original routing to Greene St, but then cut west on Walker Ave to Ashe Ave before heading south (Ashe turned into Randleman Rd); NB used Ashe up to Sycamore, then west to Eugene St, then north to Battleground Ave.
also in this timeframe it appears US 220 was straightened out in the NC 68 and NC 65 areas, removing all multiplexes. 

In 1962 or 1963, US 220 received its Mayodan-Madison Bypass, leaving behind US 220 Business.. 

Between 1964-66, US 220 was given its Stoneville Bypass, leaving behind an unnumbered route, which later became an extended US 220 Business and is again unnumbered today.  

Between 1967-68,US 220 was given a newly constructed freeway bypass of Ulah and Asheboro. The old route through these places became US 220 Business. The freeway ran only from NC 134 to Balfour, and US 220 used non-freeway Vision Dr to get back to Fayetteville St.  

In 1969-70, US 220 multiplexed with I-85 from Randleman Rd. to US 29 North on Henry Blvd, then used Wendover Ave to get back west to Battleground Ave. The surface streets through downtown Greensboro became (and remain) unnumbered.  

Between 1972-79, the freeway in Asheboro was extended to Level Cross, leaving behind more of today's US 220 Business. Mainline US 220 used Branson Mill Rd to cut from the freeway to Randleman Rd.
Also, US 220 was extended south to US 1 as new construction, leaving behind Ellerbe Rd.  

In 1980, A new US 220 freeway was built between Steeds and Emery, bypassing Star, Biscoe, and Candor. The old route through these places became US 220-A.  

In 1981-83, the US 220 freeway was extended north from Level Cross to I-85. This time, the old US 220 became unnumbered Randleman Rd.  

In 1995, the US 220 freeway was extended north past I-85/US 29-70 to I-40, then multiplexed with I-40 east back to I-85.  

In 1996, US 220 was moved onto new freeway construction between NC 134 and Steeds, bypassing Seagrove. The old part of US 220 became an extended US 220-A. This new freeway was also the beginning of I-73/74 being physically present in North Carolina.  

A new freeway bypass of Norman and Ellerbe is now under construction (so says the 2005 RMcN), which will also be part of I-73/74. The old route could be more US 220-A or just NC 73 -- we'll just have to wait and see.
With the completion of the Ellerbe section, US 220 will be 4-lane throughout N.C. except for a small section around the Summerfield area. I'm guessing when I-73 is built in this area one fine day, this will be resolved.
Coupled with US 29, US 220 makes a pretty direct alternative from Washington DC to Florence, SC and points on I-95 further south (using either US 1 and US 52 or US 74 and NC/SC 38).
I always thought it would be good to extend US 220 down to SC 9 and then east to the Myrtle Beach area.
Other than the older section of freeway around Asheboro, the freeway portions of US 220 are extremely boring.
An alternate route for US 220 to avoid Greensboro would be via NC 68, which is posted as TO US 220 north of I-40. Lou Corsaro reports this is currently faster.
Lou Corsaro and Eric Smith have US 220 on their expressways page: link.