The original N.C. 107 from the early 1920s ran from N.C. 10/U.S. 19 near Bryson City (in the settlement of Ela, actually) northeast to Cherokee, and further north along Newfound Gap Road through the Smokies into Tennessee. What we now call 107 (Sylva to Cashiers and S.C.) had been the original N.C. 106. 

In 1939 or early 1940, 107 south of Cherokee was redirected southeast to Sylva. It was signed over what had previously been N.C. 107E (see below) and U.S. 19 (the original 19 became 19A at this time), and what are now various parts of U.S. 23, 74 and 441. The little stretch of the original 107 from Cherokee southwest to Ela became part of an extended N.C. 28.  
From Sylva, 107 replaced the original N.C. 106's route from Sylva south to Cashiers and into South Carolina. All this meant that 107 had become a rare border-to-border state highway. The map at right from the 1940 RMcN atlas shows this alignment, which would last for about 10 years. 

When U.S. 441 was first designated in North Carolina around 1951, it replaced 107 north of Sylva. (Some mid-1950s commercial maps, but not the official maps from the state, show a 107/441 multiplex persevering along Newfound Gap Road.) 107 has ended in Sylva since then. 

The four-lane section was built from Sylva halfway south to Cullowhee in the early 1970s, and completely to Cullowhee in the early 1980s. The older 107 clings much more closely to the Tuckaseegee in the Cullowhee area.

107E is the only state highway known to have carried a letter designation other than "A". Of course there are U.S. 19E and 19W, but no other such state routes.