Modern-day Defiance College began as the Defiance Female Seminary in 1850. The United Church of Christ created this institution to provide schooling for young women. The school struggled financially early in its history. Local businessman William Curtis Holgate donated much of the land that Defiance College rests on today. In 1903, the Defiance Female Seminary formally became Defiance College. It is one of only two religious-affiliated colleges to begin operation in Ohio during the twentieth century.
Today, Defiance College continues to be affiliated with the United Church of Christ. Both men and women of all religious backgrounds are welcomed at the institution. Defiance College emphasizes service learning and requires all of its students to participate in community service activities in order to graduate. In 2005, the college boasted an enrollment of just over one thousand students. This same year, Defiance College had forty-one undergraduate majors and offered masters degrees in education and in business.