The University of Western São Paulo (Unoeste) was born from the dream of professors Agripino de Oliveira Lima Filho and Ana Cardoso Maia de Oliveira Lima to offer excellent higher education in Presidente Prudente and the surrounding region. This became a reality with Decree No. 71,190 of October 3, 1972, which authorized the Faculty of Arts, Sciences, Letters, and Education of Presidente Prudente (Faclepp), of the Prudentina Association of Education and Culture (Apec). In the first entrance exam, 536 candidates applied for the 350 spots offered in the three precursor undergraduate programs: Social Studies, Letters, and Pedagogy. The inaugural class was provisionally held at Colégio Cristo Rei on October 21 of that same year.

In February 1973, the first APEC building, Block A, emerged. Due to the founders' ideals and the strong demand for other fields of study in the region, the following years saw the establishment of the faculties of Health, Civil Engineering, Computer Science, and other higher education programs, as well as clinics, laboratories, and the Sports Palace. This rapidly led to the emergence of the building complex that makes up Campus 1 in Jardim Bongiovani.

In 1987, Campus 2 opened, offering programs in Agricultural Sciences, Humanities, and Applied Social Sciences. That same year, Unoeste was accredited by the Ministry of Education (MEC) as a university and expanded its knowledge with its vast infrastructure, including clinics, a veterinary hospital, an experimental farm, laboratory buildings, agronomic and zootechnical centers, and other areas dedicated to teaching, research, and the ongoing practice of citizenship. Therefore, Unoeste is the only private higher education institution in western São Paulo with the status of university.

In addition to Prudente, Unoeste also operates in Jaú and Guarujá. In August 2018, it began operating the first medical school in Jaú, initially in an area adjacent to Thereza Perlatti Hospital. However, in February 2021, it opened a new campus near Território do Calçado Shopping Mall. On the São Paulo coast, medical school programs began in March 2019, on a floor adjacent to Santo Amaro Hospital. By August 2021, the new campus, located in the Enseada neighborhood, was already receiving partial activities. Thus, Unoeste is already recognized as the most modern academic facility in the Jaú and Baixada Santista regions.

The Universidade do Oeste Paulista also offers distance learning (EAD) courses in almost every state. With the same excellence in this teaching modality, undergraduate, specialization, and MBA programs are offered at more than 110 on-site support centers throughout the country, in addition to an international center in Japan .