Conodoguinet Creek, a tributary of the Susquehanna River, crosses the southern part of the township just north of Carlisle, making several large bends.

[3] A portion of the Carlisle Indian Industrial School National Historic Landmark is in the township.

In the mid 18th century, the area that is now the township was inhabited primarily by Scotch Irish settlers who were granted land patents in that region by the family of William Penn, the proprietors of Pennsylvania at the time.

The rapid settlement of this area at that time was the result of the Penns' plan to keep the Scotch Irish who were viewed as rowdy and unsophisticated out of the more refined Lancaster and York counties to the southeast.

[citation needed] Thus, by the late 1700s, the population west of the Susquehanna River was composed almost exclusively of Scotch Irish settlers.

As was common of most areas in the Cumberland Valley at that time, most early settlers of North Middleton Township were farmers by trade, and perhaps the area's most lasting legacy was the great quantity and quality of barns built there.

Much of the Carlisle Barracks property is in North Middleton Township, and this includes the census-designated place.