Depending on who you believe, US 401 has existed two separate times in Wake County.  A few maps from the mid-1930s indicate that a US 401 ran as far north as downtown Raleigh, along what's now South Saunders Street and South Wilmington Street.  Within a few years, US 15A took over the routing (assuming, of course, that 401 actually held this routing), and nothing in the county was designated as 401 by 1938. Making this more confusing is that other maps consistently marked the route as 15A the entire time.

In any case, US 401 was (re-)designated along its current route in 1956.  The new designation eliminated US 15A as far north as Garner, and NC 59 from Raleigh north.  The route hasn't changed much since then; the only significant rerouting was a two-mile stretch in the late 1960s that is now a city road (Kyle Drive) in north Raleigh.

Like all other US and NC routes, US 401 was signed along the Beltline for a few years in the late '80s and early '90s, but it was the first highway that was put back on a routing through downtown Raleigh, in 1993.

US 401 is the only multi-lane highway through southern Wake County between I-40 and US 1, and as such it carries much more traffic than it is designed for.  The congestion is heaviest in the vicinity of Wake Technical Community College, halfway between Fuquay-Varina and Garner.

The Big Man, a minor local landmark for thirty years on a site near the interchange of US 401 and I-540, was perhaps the most recognizable feature along US 401.  After the Big Man's owner sold his land, he relocated to a home near the interchange of I-540 and Capital Boulevard (if you know where to look, it's fairly easy to see from westbound 540).

US 401 was widened to four lanes divided from Garner to Fuquay-Varina in 1996-97, and a six-lane widening from the US 1/401 split north to the Neuse River was completed in early 2003. This leaves only the short section south of Fuquay-Varina and the stretch from the Neuse through Rolesville to Franklin County as the only remaining 2-lane sections of 401 in the county.

The widening of the northern part of 401, which will continue north to Louisburg in Franklin County, will contain a bypass to the southeast of Rolesville.  It is unknown if the road will be widened to four (more likely) or six lanes, or if the existing US 401 in Rolesville will be redesignated a Business route or lose its US route status altogether. Construction on the bypass is temporarily scheduled to begin in 2012.