New England manufacturing declined in the 20th century, however, particularly during the Great Depression.

Keene became a manufacturing center for wooden-ware, pails, chairs, sashes, shutters, doors, pottery, glass, soap, woolen textiles, shoes, saddles, mowing machines, carriages and sleighs. Keene was incorporated as a city in 1874, and by 1880 had a population of 6,784.

Keene's manufacturing success was brought on in part by its importance as a railroad city, being the meeting place of the Cheshire Railroad, the Manchester & Keene Railroad, and the Ashuelot Railroad.

An example is the Keene Public Library, which occupies a Second Empire mansion built about 1869 by manufacturer Henry Colony.

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Land was set off for the towns of Sullivan and Roxbury, although Keene would annex 154 acres (0.62 km Timothy Dwight, the Yale president who chronicled his travels, called the town "..of the prettiest in New England." Situated on an ancient lake bed surrounded by hills, the valley with fertile meadows was excellent for farming.

A historic seaport and popular summer tourist destination, Portsmouth was the home of the Strategic Air Command's Pease Air Force Base, later converted to Portsmouth International Airport at Pease with limited commercial air service.

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