The Connecticut is one of New England's earliest developed rivers, with European settlements that go back over 350 years. The early history of the Valley can still be seen at the Griswold Inn (1776) in Essex, CT, the Wadsworth Atheneum (1842) in Hartford, CT, Historic Deerfield (1717-1824) in Deerfield, MA, the Cornish, NH-Windsor, VT Bridge (1866, the longest covered bridge in the U.S.), and Bullfinch Row (1773-1839), seven Federal and Greek Revival houses in Orford, NH.

The Industrial Revolution flowered in the Valley, nourished by water power, prosperous, stable communities, and good old "Yankee ingenuity." Precision engineering originated here, evidenced today by the Springfield Armory, the Colt firearms factory at Hartford, CT and the American Precision Museum at Windsor, VT. Holyoke, MA was one of the first planned industrial communities in the U.S., utilizing three levels of canals (1849-91) to deliver waterpower from the Holyoke Dam to industrial mills in the city.

The roster of American leaders in the arts and letters whose lives are part of the Valley's history include: Mark Twain, Harriet Beecher Stowe, Emily Dickinson, Wallace Stevens, Childe Hassam, Augustus Saint-Gaudens, Maxfield Parrish, Roger Tory Peterson, and Dr. Seuss (Theodore Giesel).

The Valley is home to a host of universities, colleges, museums, and cultural facilities. These include: the University of Massachusetts; Smith, Mount Holyoke, Amherst, Trinity, Dartmouth and Weselyan colleges; the Connecticut River Museum, the Science Center of Connecticut (Hartford), and Springfield Science Museum, the Montshire Museum, the Goodspeed Opera House, and the Basketball and Volley Ball Halls of Fame.