Running through the center of the state, it travels nearly the entire length of Vermont and is 216.666 miles (349 km) long.

The road is the main thoroughfare for some of Vermont's most well-known resort towns, including Wilmington, Ludlow, Killington, Warren, and Stowe.

VT 100 is a popular tourist route during the fall (for foliage) and winter (for skiing), and can be heavily trafficked during those seasons.

Despite this, the road retains a rural feel through most of the towns it traverses and is relatively free of development, except for some of the areas around the ski resorts.

Several of the most heavily traveled sections of VT 100 (such as the section between Waterbury and Stowe and Warren to Waitsfield) were in very poor condition due to state and local road maintenance budget shortfalls, recent harsh winters and heavy damage by Tropical Storm Irene in 2011; since that storm, the state has undertaken the reconstruction of many segments of the road.