The Dayton and Michigan Railroad provided the single most important impetus to the growth and development of Wapakoneta. Although Wapakoneta had been platted in 1833, at the time of incorporation (1848), "the town was still without any material improvement worth the name of enterprise, save in the erection of residences and opening of small retail stores and shops." On March 15, 1854, in its first ordinance, the village council of Wapakoneta voted unanimously to grant a right-of-way to the Dayton and Michigan Railroad Company to construct a railroad line through the community. The financial backers of the railroad ran short of funds during construction, and planned to end the line at Sidney, but local leaders raised $70,000 to ensure its extension.
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The Dayton and Michigan Railroad began operation in 1858, giving the people of Wapakoneta "their first railway connection with the outer world." It was the first railroad in Auglaize County and the first north-south line in western Ohio. With a route stretching from Lake Erie to the Ohio River, the railroad allowed local farmers and industrialists to ship their products and goods throughout the country, promoting economic development. Within a few years of the railroad's completion, many industrial enterprises were established, as well as two large grain warehouses. As business grew and employment opportunities expanded, the population of Wapakoneta more than doubled from 900 to 2,150 between 1860 and 1870, the largest period of growth in the community's history. In later years, the railroad line would be known as the Cincinnati, Hamilton, and Dayton Railroad, Baltimore and Ohio Railroad, Chessie System, and CSX.