On December 30, 1949, under the agreements of the French–Vietnamese Cultural Treaty, the Indochinese University was reorganized into the Franco–Vietnamese Joint University, renamed the University of Hanoi, consisting of two centers: one in Hanoi and one in Saigon. The University began operating in January 1951 under the leadership of a French Rector, assisted by a Vietnamese Vice-Rector.

On November 12, 1953, a joint document signed by the Governments of France and Vietnam renamed the College of Science to the Faculty of Science of the University.

In November 1954, the center in Hanoi moved south and merged with the center in Saigon. Initially, it consisted of the following schools: Faculty of Law, Joint Faculty of Medicine–Pharmacy, Faculty of Science, College of Architecture, and the Preparatory School of Letters. The French–Vietnamese Cultural Treaty (December 30, 1949) and its supplementary agreement (January 8, 1951) stipulated that administrative authority would be transferred from the French Government to Vietnam. On May 11, 1955, the transfer ceremony from the French Government to the Vietnamese Government took place. This date became the milestone marking the establishment of the National University of Vietnam. The National University of Vietnam was administered by a Vietnamese Rector. Under Decree No. 247 dated April 28, 1955, Professor Nguyễn Quang Trình, Full Professor and Doctor of Science, was appointed Rector of the National University. At the same time, Professor Nguyễn Quang Trình was appointed Acting Dean of the Faculty of Science (formerly the College of Science).

On December 22, 1955, the opening ceremony of the University took place after the official transfer. As of January 1, 1956, the Faculty of Science had 743 students and 15 professors (including 7 French professors). The final examinations of the 1955–1956 academic year, First Session (today considered the first sitting), began on June 11, 1956, with 96 students passing out of 326 candidates. The Second Session, beginning on October 16, 1956, saw 84 students passing out of 241 candidates.

In March 1957, after the establishment of Huế University, the National University of Vietnam was renamed Saigon University; accordingly, the Faculty of Science adopted the name Saigon University of Science.

On Tuesday, October 13, 1964, at 9:00 AM, the groundbreaking ceremony for the construction of the building of the Saigon University of Science at the Thủ Đức University campus (now the Linh Trung campus) took place under the Cultural Aid Program of the New Zealand Government to Vietnam.

Saigon University of Science was considered the leading institution in fundamental sciences at the time and the cradle of basic scientific research. The University offered undergraduate and postgraduate programs, and in 1965 organized the defense of the first national doctoral dissertation in Chemistry. From that point, it began offering the national Doctorate and the “Third Cycle Doctorate” in scientific disciplines.

Successive Deans of the Faculty included: Prof. Dr. Sci. Lê Văn Thới (1958–1964); Prof. Dr. Sci. Dương Thị Mai (Mai Trần Ngọc Tiếng) (1964–1965); Prof. Dr. Sci. Nguyễn Chung Tú (1966–1973); Prof. Dr. Sci. Phùng Trung Ngân (1973–1975).

In April 1975, when the South of Vietnam was completely liberated, the Faculty of Science was renamed the University of Science, operated by an Interim Management Committee led by Prof. Dr. Nguyễn Hữu Chí until 1977.

Ho Chi Minh City University of General Sciences

In 1977, Ho Chi Minh City University of General Sciences was established on the basis of merging the University of Science and the University of Letters. Associate Professor Dr. Lý Hòa was appointed Rector by the Prime Minister (1977–1990). In 1990, Prof. Dr. Nguyễn Ngọc Giao was appointed Rector by the Ministry of Education and Training (1990–1994), continuing until 1996.

The University consisted of 16 faculties: Mathematics, Physics, Chemistry, Biology, Geography, Geology, Literature, History, Philosophy, Economics, Library Science, English, French, Russian, Law, and Oriental Studies. There were also seven research–service–production centers.

On January 27, 1995, Vietnam National University Ho Chi Minh City (VNU-HCM) was established, and the University of General Sciences became one of its member institutions.

The University played a major role in training thousands of young scientists in both the natural and social sciences. It maintained relationships with dozens of universities, institutes, and educational organizations worldwide, and organized numerous scientific conferences as well as staff exchanges and professional training programs.

University of Science, VNU-HCM

The University of Science was established on March 30, 1996, following the restructuring of Ho Chi Minh City University of General Sciences, and became a member university of VNU-HCM. Prof. Dr. Nguyễn Văn Đến served as the first Rector (1996–2000). From 2001 to 2010, Assoc. Prof. Dr. Dương Ái Phương served as Rector. Subsequently, Prof. Dr. Trần Linh Thước held the position from 2011 to 2020.

Since 2021, Assoc. Prof. Dr. Trần Lê Quan has been serving as Rector.