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Odessa's early history began in the 1660s when the Dutch settled the Appoquinimink area and adopted the Indian name for the area, "Apequinemy." Its location along the river gave hopes of establishing a trading route with colonies to the west. The English began to colonize the region and peacefully gained control in 1664. The British granted the previously held Dutch area to Captain Edmund Cantwell, the first sheriff of New Castle County under the government of William Penn.
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The historic atmosphere of Odessa is the town's most prominent characteristic.The historic district and several individual buildings are on the National Register of Historic Places. In 1731, Richard Cantwell erected a toll bridge over the Appoquinimink Creek, called Cantwell's Bridge, and the town took the same name. In 1767, William Corbit opened the first industry in the town, a tannery. 1817 saw a blacksmith shop established, and in 1855 bank was incorporated. Later industries included fertilizers, fruit drying and canning.
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