The Academy of Neuchatel was founded in 1838. It owes its birth not only to the strong political will to provide the region with a high quality educational establishment, but also to the geologist and paleontologist Louis Agassiz who made significant scientific advances at the time.

In 1866, the Academy was comprised of the Faculty of Arts, the Faculty of Science and the Faculty of Law, as well as some high school level institutions. In 1873, the Faculty of Theology was added. By decree of the Grand Council of 18 May 1909, the Academy of Neuchatel was officially established as the University of Neuchatel.

In addition to the institution's renaming, the 1910 law on Higher Education created a business school, and gave students the opportunity to undertake doctoral study in all faculties. Since its establishment, the UniNE has always aimed to provide education at the highest possible level. Its modest size lends it the dynamism and flexibility needed to achieve this goal.