Its number is derived from its original 1922 designation as New England Interstate Route 12 (also known as the "Keene Way").

The 283.3-mile (455.9 km) four-state series of State Route 12s extend from Morrisville, Vermont, to Groton, Connecticut.

NH 12 begins in Fitzwilliam where it connects to Massachusetts Route 12 at the state line.

NH 12 continues northwest through Troy, then dips into parts of Marlborough and Swanzey before entering the city of Keene.

NH 12 enters the southwestern corner of Surry, then turns nearly due west, crossing into the town of Westmoreland.

It intersects the northern terminus of NH 63 near the Connecticut River, then turns north and enters Walpole.

Now paralleling the eastern bank of the river, NH 12 heads north towards the town center.

The highway continues through downtown, then intersects NH 11, which connects to Interstate 91 and US 5 in nearby Springfield, Vermont.

New Hampshire Route 12A is a designation held by two state highways which bypass separate sections of NH 12.

The highway initially heads northeast, then turns north to parallel the Ashuelot River and enters the town of Surry.

It runs along the eastern side of the Connecticut River, bypassing downtown Claremont to the west.

NH 12A continues through western Plainfield without any major junctions, then enters the city of Lebanon.