US 301 was established in 1932 as a replacement of the piece of US 17-1 north of Wilson and the whole of US 217. Thus US 301 initially ran from US 17 (now US 76) at Pee Dee, South Carolina northeast through Dillon, Lumberton, Fayetteville, Dunn, Smithfield, Wilson, Rocky Mount, and Emporia, ending at US 1 in Petersburg, Virginia. This entire route is now paralleled by Interstate 95. US 301 was at one time alternately referred to as Federal Route No. 301 early in its existence.