The University charter was laid down by two Presidential Decrees, P.D. 1434 and P.D. 1437. On June 10, 1978, then President Ferdinand E. Marcos issued P.D. 1434 which established the Isabela State University by merging the Isabela State College of Agriculture (ISCA) at Echague, the Cagayan Valley Institute of Technology (CVIT) at Cabagan, and absorbing the college courses of the Isabela School of Arts and Trades (ISAT) in Ilagan, Roxas Memorial Agricultural and Industrial School (RMAIS) in Roxas, San Mateo Vocational and Industrial School (SMVIS) in San Mateo and Jones Rural School (JRS) in Jones, Isabela. The merger, likewise, identified Echague to serve as the main campus and administrative site.

In 1999, the CHED Memorandum Order No. 18, s. 1999 which provides the guidelines for the integration of CHED Supervised Institutions (CSIs) to SUCs was enacted. Pursuant to this Order, the first CHED-supervised Institution that was integrated to the University is the Cauayan Polytechnic College at Cauayan, Isabela. In 2002, two CSIs were again merged into the system, namely: Delfin Albano Memorial Institute of Agriculture and Technology (DAMIAT) in San Mariano; and the Angadanan Agro-Industrial College (AAIC) in Angadanan, Isabela. Responding on the request of the provincial government of Isabela, the University extended its academic programs in Palanan effective first semester of Academic Year 2005-2006. Not long after, and through the collaborative efforts of University officials and the local governments of the City of Santiago.

To date, the Isabela State University system maintains nine campuses and three satellite extension campuses (with the addition of the Aurora Extension Unit) that are strategically positioned in Isabela, the second largest province in the country, comprising of 34 municipalities and 3 cities: 1 independent and 2 component cities. These campuses are also straddling along the Region’s “Midrib-Peripheral Growth Centers and Socio-Economic Development Zone” where the major urban and commercial centers of the region ply their trades. This is aside from having an edge of strategic proximity to the site of the Regional Agro-Industrial Center in Cauayan City, and its accessibility to Santa Ana in Cagayan, a special economic zone and entry point of International trade in Cagayan Valley. Likewise, the campuses lie within the periphery of Tuguegarao and Santiago Cities, respectively.

Forty years since its inception, the University has undoubtedly metamorphosed into a highly credible Higher Education Institution (HEI).

Its enrollment is remarkably and consistently increasing, though its momentum was interrupted by the implementation of the K-to-12 Program. It is, likewise, continuously producing national topnotchers in licensure examinations. The Isabela State University (ISU) is a SUC Level IV Higher Education Institution (HEI) situated in North-eastern Philippines, particularly in the Cagayan Valley-Region 02. It is a certified ISO 9001:2015-Quality Management System for the Provision of Instruction, Research and Development for Higher and Advanced Education, by TÜV SÜD Asia Pacific.

The University also banners compliance to the Freedom-of-Information. At the same time, ISU houses the Special Economic Zone (SEZ) Institute for Region 02. The University envisions as one of the leading research universities in the ASEAN Region by 2024. The University as well faithfully embarks in its mission to develop globally competitive human, technological resources and services through quality instruction, innovative research, responsive community engagement and viable resource management programs for inclusive growth and sustainable development.