It connects the town of Ossipee in east-central New Hampshire with Salem on the Massachusetts border, while passing through Manchester, the largest city in the state.

At Main Street it meets the southern terminus of New Hampshire 28 Bypass, and Rockingham Road makes a hard left turn, heading slightly southwest.

At Webster Street, NH 28 joins U.S. Route 3 for a concurrency along Daniel Webster Highway, leaving at Manchester's northeastern corner to the village of South Hooksett within the town of Hooksett, where it has another interchange with I-93 (exit 9) at the city line.

Both NH 28A (Mammoth Road) and New Hampshire 28 Bypass (Londonderry Turnpike) have their northern termini within Hooksett.

Leaving US 3 along Pinewood Road just before the Suncook River, NH 28 heads off in a northeasterly direction towards the main village of Allenstown before crossing the Suncook River and going through the extreme eastern corner of Pembroke and entering the town of Epsom.

In the main village of Epsom, it meets US 202/US 4/NH 9 (Franklin Pierce Highway) at a large traffic circle.

In Alton, Suncook Valley Road meets its northern terminus in the main village of Alton at a traffic circle with NH 11/NH 28A, leaving the traffic circle along Wolfeboro Highway, going north, and then northeast, roughly following the eastern shore of Lake Winnipesaukee, meeting the northern end of NH 28A about halfway to the South Wolfeboro village of the town of Wolfeboro.

In the village of Wolfeboro Center, just north of Lake Wentworth, NH 109 leaves to the southeast along Governor John Wentworth Highway, while NH 28 continues straight along Center Street to the northeast.

The southern segment of NH 28A, 7.623 miles (12.268 km) in length and locally named Mammoth Road, connects Londonderry and Hooksett, running through the eastern suburbs of Manchester.