On March 12, 1903, the legislature authorized founding of the University of Puerto Rico, and that day the "Escuela Normal" was proclaimed as its first department.

1928 – The San Felipe Segundo hurricane struck the island of Puerto Rico and caused serious damage in the Río Piedras campus.

1935 – The U.S. Congress extended to Puerto Rico the benefits of Bankhead-Jones Act, which provided funding for research and the construction of more buildings.

1936–1939 – Major structures in Spanish Renaissance style are built in the quadrangle in Río Piedras, including buildings such as the Tower Theatre.

1938 – Augusto Rodríguez composed the music and lyrics Arriví Francisco's Alma Mater, the university anthem.

July 2010, the Middle States Commission on Higher Education placed the accreditation of the university on probation citing concerns about shortfalls in the governance of the institution.

2017 – The UPR's staff organized a strike in opposition to budget cuts proposed by the Financial Oversight and Management Board for Puerto Rico.

[11] The hurricane also affected the process of accreditation since eight campuses where in non compliance according to of the Middle States Commission on Higher Education.

[12] The eleven campuses opened within two months of Hurricane Maria, offering a sense of structure and normalcy for professors and students.

[13] 2019– During Jorge Haddock tenure the university newspaper, Diálogo, after 32 years in print, was moved online and employees were laid off until only the editor and an assistant remained.

[14] 2021 – In June the Financial Oversight and Management Board cut $94 million from the UPR budget which would have drastically affected the institutions ability to operate.

On April 30, 2013, governor Alejandro García Padilla signed into law Act 13 of 2014 enacted by the 17th Legislative Assembly.

UPR has the highest selectivity index of all colleges and universities in Puerto Rico,[citation needed] it has also maintained a systemwide admission rate of 67% since 1997.

[30] On August 24, 2020, the university announced ten investigations for preventing and mitigating the spread of COVID-19 as part of $1.7 million the institution received from the local government.

[42] Research activity, measured in terms of external funds received, has grown exponentially since 1985, doubling every five years.