On August 8, 1794, General Anthony Wayne and his soldiers arrived at the confluence of the Maumee and Auglaize Rivers and built the fort called "Fort Defiance." During the War of 1812, Fort Winchester was built near this same site.
In 1803, Ohio was the first state carved from the Northwest Territory. The organization of Defiance County began on February 12, 1820, when the Ohio Legislature passed an Act. The Act provided that all the land in the State of Ohio yielded by the Indians to the United States was to become 14 separate counties. Originally, Williams County, organized April 1824, occupied the northwest corner of the State, but included most of the area that is now Defiance County. January 13, 1825, after a resolution passed the Ohio Legislature, the town of Defiance was established as the Seat of Justice for the County of Williams. There was great dissatisfaction in Defiance after the Michigan boundary settlement in 1836 which added about 150 square miles to the north end of Williams County and the village of Defiance became more of a border town. In 1846, Bryan became the County seat, much to the dissatisfaction of the people of Defiance, as it was located near the center of the county.
A petition was prepared in December 1844, and circulated. The Legislature passed the bill March 4, 1845, which provided for parts of Williams, Henry and Paulding counties to become a separate county to be named Defiance County. The bill also provided that the Seat of Justice would be established at the town of Defiance.
At the next session of the Legislature, an unsuccessful effort by the residents of Williams County was made to have the action that established Defiance County repealed.
The afternoon of March 13, 1845, at "Old Fort Defiance" a celebration of the erection of Defiance County was held. Despite high waters and bad roads, a large number of people attended the event.
The first term of court in the newly established Defiance County was opened April 2, 1845. The first County Commissioners were appointed by the Court of Common Pleas on April 3, 1845, and served until December 1, 1845. A special election for county officers was held April 15, 1845, and October 14, 1845, and officers were elected.
The canal system was an important part in the development of Defiance County. In 1825 construction of the Miami & Erie Canal began and it was completed in 1929. Then, in 1837 construction of the Wabash & Erie Canal began. By 1845, a canal system was completed which connected Defiance with Toledo, Cincinnati, and Fort Wayne. The first train came to Defiance in 1852 and by 1860 the train had replaced the canals as the primary source of transportation.
Out of the Great Black Swamp has emerged businesses of varying sizes and types, but much of the county is flat or gently rolling farmland.