Manasseh Cutler generally receives credit for establishing Ohio University at Athens, Ohio in 1804. Cutler and the other investors in the Ohio Company of Associates followed the terms of the Northwest Ordinance of 1787 and set aside land for the establishment of a public university. Cutler was a graduate of Yale University and he used that school's charter as a model for Ohio University. On January 8, 1802, the legislature of the Northwest Territory and Governor Arthur St. Clair approved the charter of the American Western University. This institution of higher education was never opened.

On February 18, 1804, the Ohio legislature approved a new act, establishing Ohio University at Athens. Ohio University first offered classes in 1809. Originally, Ohio University offered more of a high school course of study rather than a college education. The main reason for this was the lack of a skilled faculty. Rather than consisting of specialists in their respective fields, the instructors at Ohio University generally had a basic education in a wide variety of topics. In 1822, Ohio University began to offer a traditional college program.

Throughout the nineteenth century, Ohio University continued to grow. By the late 1800s, Ohio University had taken a leading role in providing education and training to Ohio's future teachers. The goals of the university and the State of Ohio were to provide skilled teachers and to establish standards in public education. In 1896, the Ohio government provided Ohio University with government funding through taxation. Ohio University was one of the earliest institutions of higher education in Ohio to receive some state support through taxation. Today, Ohio University has an enrollment of more than 28,000 students and offers 276 different undergraduate degree programs.