The North Appalachian Experimental Watershed (NAEW) in Ohio was established in 1935 to improve economical and physical sustainability in agriculture. The objectives were to test management practices on small watersheds, investigate scaling of runoff and erosion to larger areas, and research ways to extrapolate the results to ungauged areas. The facility was equipped with a permanent infrastructure consisting of runoff stations and rain gauges for watersheds ranging in size from 0.26 to 1854 ha, and 11 large (0.008 ha) monolith lysimeters to investigate small-scale water balances, all in an area greater than 2000 ha. After about 1970, the NAEW was reduced in size to 425 ha consisting of mostly small watersheds (“test beds”) ranging in size from 0.26 to 3.07 ha. The NAEW was in operation for approximately 81 years generating a long record of runoff and other data for various watersheds, and closed in 2015. A wide variety of experiments were conducted on the NAEW with many high-impact accomplishments and addressing emerging issues that founders never envisioned. Nearly, 500 publications came from investigations during the history of the facility, and insights for establishing new experimental watersheds are presented covering site selection, funding, site specificity, extrapolation of results, generation of runoff in different physiographic regions, collaboration, off-site investigations, and instrumentation. The research on water quality was added to the research objectives in the 1970s, including nutrients (nitrogen and phosphorus) and pesticides in surface runoff and subsurface flow.