The university's origins date back to the opening of Wrexham School of Science and Art (WSSA) in 1887. At this time John Viriamu Jones called for a University of Wales. The WSSA began offering University of London-validated degrees in science in 1924. The original name of Wrexham School of Science and Art was changed several times. In 1927, it became Denbighshire Technical Institute, becoming Denbighshire Technical College in 1939 and North East Wales Institute of Higher Education in 1975 by the merger of Denbighshire Technical College, Cartrefle Teacher Training College and Kelsterton College of Connah's Quay, Deeside. Initially, its degrees were validated by the University of Salford. Some famous alumni include Andrew Gwynne (when it was North East Wales Institute of Higher Education), Gavin Roberts, and Brian Percival (as North Wales School of Art and Design).

In 1993, NEWI became an associate member of the University of Wales and all further education courses in Wrexham were moved to Yale College, Wrexham (now part of Coleg Cambria). In 2004, NEWI became a full member of the University of Wales, with "University of Wales, Wrexham" touted as a potential future name, and in 2006 became accredited by the University of Wales and exercised devolved powers to validate and deliver its own degrees. The university was officially renamed "Glyndŵr University" in July 2008 after being granted degree awarding powers. The university was visited by the Queen in 2003 and by Birgitte, Duchess of Gloucester in 2005.

In June 2014, the Home Office suspended the University's authorisation to sponsor international students.

On 24 November 2014 Glyndŵr University has had its right to sponsor international students reinstated by the Home Office.

In 2016, the university underwent a minor name change and is now called "Wrexham Glyndŵr University" in English, and "Prifysgol Glyndŵr Wrecsam" in Welsh.

Between 2008 and 2019, the main Wrexham campus of the University hosted Wales Comic Con until it moved to Telford, but returned for a one-day event in 2022.

In August 2022, the university announced it was considering re-naming itself to "Wrexham University" (Welsh: Prifysgol Wrecsam) dropping "Glyndŵr" from its name. On 27 April 2023, the university confirmed its plans to rename to "Wrexham University", following consultations with staff, students and other organisations, and approval by the Privy Council. The university stated the increased attention of Wrexham due to Wrexham A.F.C., Welcome to Wrexham and Wrexham's awarded city status, as reasons for the move. The rebrand is expected to take place between the end of 2023 and early 2024. The university will also make plans to "continue celebrat[ing] [Glyndŵr's] legacy".