Massie's Station was the first permanent settlement in the Virginia Military District of the Northwest Territory in the years after the American Revolution. It was laid out along the Ohio River in 1790 near three islands. American Indians used these islands to attack settlers traveling down the Ohio River. Numerous people lost their lives in these attacks. The community was named after Nathaniel Massie, an explorer and entrepreneur who helped survey the Virginia Military District. Massie offered nineteen men property if they would settle in the town. He used the settlement as a base for his survey work in the district. In 1791, Massie's Station became known as Manchester, Ohio. Massie named the community after Manchester, England. It was the fourth permanent settlement established in the Northwest Territory. By 1791, residents had completely encircled the community with a stockade to provide protection from American Indians. This was the last town in what would become Ohio to be enclosed with fortifications. Manchester served as the county seat for Adams County from 1797 to 1803, when residents moved local government to West Union.
Located on the Ohio River across from the slaveholding state of Kentucky, Manchester was an important stop along the Underground Railroad. African-American slaves seeking freedom in the North commonly found aid among the town's residents during the first part of the nineteenth century. The town also prospered as a stop for steamboats as they traveled along the Ohio River. Most industries in the community were linked to agriculture. During the nineteenth century, a tobacco warehouse, pork-processing company, a buggy manufacturer, a mill, and a nursery operated in Manchester for varying lengths of time. By the 1840s, Manchester had become the largest town in Adams County.
In 1908, the Manchester Button Factory began operation. It was located in the town due to the abundance of mussels in the Ohio River, which could be used to manufacture the buttons. At its peak, the plant employed 125 men. In 1934, Alfred Holbrook College moved to the town from Lebanon, Ohio. It operated for only seven years. Manchester remains a relatively small community today. In 1990, just over two thousand people lived in the town. In August, Manchester hosts the "Kinfolk's Landing Days," a festival that celebrates the town's history as an important stop on the Ohio River.