The section from Portsmouth to Milton is a controlled-access toll highway known as the Spaulding Turnpike.

The southern terminus of NH 16 is at the Portsmouth Traffic Circle, intersecting with Interstate 95 and US 1 Byp..

From Milton, NH 16 continues north as a two-lane expressway, roughly paralleling the Maine border.

From Errol NH 16 continues northeast to Wentworth Location and the Maine border.

After crossing the border the road becomes Maine State Route 16 and heads east toward Rangeley.

[3] In 1926, the New England road marking system was superseded by the system of United States Numbered Highways, and many of the New England Routes, including NH 16, became state highways with the same number.

NH 16 formerly served as a non-tolled alternative to the Spaulding Turnpike between Dover and Rochester.

Between the Rochester/Milton town line and the northern terminus of the Spaulding Turnpike, NH 125 carries the White Mountain Highway moniker.

[5] This is a rare instance of a hidden route in New Hampshire and is interesting in that a duplicate state numbering has been given precedence over a unique federal one.

The northern segment of NH 16A is a loop road in Jackson that is 1.029 miles (1.656 km) long.

[5][6] New Hampshire Route 16B is a 5.381-mile-long (8.660 km) long state highway located entirely in Jackson.