The founder of the university, Mariano F. Jhocson Sr., established the institution on August 1, 1900, as Colegio Filipino in Quiapo, Manila.

It is considered as the first private nonsectarian and coeducational institution in the Philippines and also, the first university to use English as its medium of instruction, replacing Spanish.

[2] Only a handful of students at that time were enrolled in the fledgling school and they were in the elementary and secondary levels.

[2] From Colegio Mercantil, the Board of Trustees changed the name of the institution to National Academy in 1916.

After 21 years of service in the field of education, the Board of Trustees applied for university status to the Department of Public Instruction.

[2] Bachelor's degrees in Chemical, Electrical, Industrial, Mechanical Engineering and Architecture and Arts were opened.

The university was able to re-open its doors after three weeks of restoration work and used Mariano F. Jhocson Memorial Building.

[3] In 2008, the SM Group of Companies acquired majority ownership of National University.

As the institution grows so as their demand for a bigger campus increases which led to the birth NU Main Building Expansion.

The abandoned site of St. James College of Calamba was purchased by NU and it is now occupied by National University as a satellite campus.

In the UAAP, NU has teams participating in twelve sports out of fifteen, namely; cheerleading, basketball, indoor volleyball, beach volleyball, football, baseball, softball, tennis, table tennis, badminton, fencing, taekwondo and chess.