One of the biggest Colleges in the University of Santo Tomas, the College of Commerce was established by the Very Rev. Fr. Silvestre Sancho, O.P in 1930 as a department in the College of Education that offered a two-year associate program in Commercial Science. 

Although it remained attached to the College of Education, the department was raised to the rank of a School of Commerce in 1933, with Dr. Stanley Prescott as Director. Eventually, the College of Education granted its autonomy in 1934. Dr. Stanley Prescott was given the honor and the responsibility to be the first Dean of the College of Commerce and Rev. Fr. Ciriaco Pedrosa, O.P. as the first Regent. In 1940, during the deanship of Rev. Fr. Pedro Mateos, O.P., different fields of specialization were introduced, namely: Accounting, Management, Marketing, Economics, Banking and Finance, which were revitalized by the succeeding administrators. 

The College was forced to close during the Second World War and reopened in June 1945. Under the deanship of Dr. Mariano Apacible, the four major programs of the College namely, Accounting, Banking and Finance, Economics and Management, were fortified with pedagogy improvements. 

In 1988, the College officially became known as the College of Commerce and Accountancy. In March of 1990, the College was granted a Level II Deregulated Status by the Federation of Accrediting Agencies of the Philippines (FAAP). The Philippine Association of Colleges and Universities Committee on Accreditation (PACUCOA) granted the College a Level II Formal Status in 1993 and reaccreditation in 1998. In 1999, under the charge of Dean Amelia Halili, the College was recognized as a “Center of Development” by the Commission on Higher Education (CHED). 

In the efforts towards asserting its presence as a primary model business school in the country, and pursuant to the Commission on Higher Education’s Memorandum Number 17, the College revived its entrepreneurship program under Dean Jeanette Isabelle V. Loanzon and offered the Bachelor of Science in Commerce major in Entrepreneurship more popularly known as the Triple-E Program (“Entrepreneurship and Ethics Education towards Equity”) in AY 2004-2005 which eventually became a straight program, BS in Entrepreneurship and was initially offered in AY 2007-2008. This is an innovative program which synthesizes evidence-based practice of entrepreneurship with ethics education towards social equity. 

Meanwhile, in the year 2005 the Accountancy Department separated from the College of Commerce forming the UST Alfredo M. Velayo (AMV) -College of Accountancy. 

The latter part of the 2006-2007 academic year signaled the beginning of even more significant changes compressed in even lesser time. With Dean Helena Maria F. Cabrera at the helm, and pursuant to the Commission on Higher Education’s Memorandum Number 39, the Bachelor of Science in Commerce academic programs were gradually phased out and were replaced with the Bachelor of Science in Business Administration academic programs offering a wider range of specialized majors: Business Economics, Financial Management, Human Resource Development Management, and Marketing Management. In 2007, the BSC major in Entrepreneurship was replaced by the BS in Entrepreneurship program on a phased-in basis. 

The College celebrated its 75th Diamond Anniversary in 2008, and the administrators, academic officials, non-academic support staff and students were all geared towards a singular vision of achieving the distinction of being a model business school at about the same time when the University celebrated its quadricentennial anniversary in year 2011.The College was renamed the College of Commerce and Business Administration in the same year when the BSBA major in Financial Management and BSBA major in Marketing Management were initially offered. 

In AY 2009-2010, PACUCOA awarded the Level II First Reaccredited Status to the College for the Bachelor of Science in Business Administration Program with the following majors: Business Economics, Financial Management, Human Resource Development Management, and Marketing Management. 

Under the Deanship of Prof. Ma. Socorro P. Calara, PhD, PACUCOA awarded the Candidate Status to the College for the Bachelor of Science in Entrepreneurship program. The conferment of the Degrees of Bachelor of Science in Entrepreneurship, as well as BSBA major in Human Resource Development Management and BSBA major in Business Economics to their first batch of graduates, coincided with the Quadricentennial Anniversary of the University in 2011. 

In AY 2011-2012, the College took a significant leap by offering the straight BSBA programs. With this move, students had to select a particular major from the time of admission application. Upon acceptance, instead of engaging in two years of Pre-Commerce, students enrolled directly to their choice of BSBA major from their freshman year. 

It was also around this time when the College linked up with the Junior Achievement of the Philippines (JAPI) to enhance and to strengthen the curriculum of the BSBA-major in Marketing Management Program in order to prepare the graduates of the program to successfully pass the certification examination to become a Registered Marketing Professional. 

The BS Entrepreneurship program was first granted Level I Formal Accredited Status by PACUCOA in January 2013. In keeping with its vision of being a model business school, the College, spearheaded by Dean Mary Hildence M. Baluyot, has received Level III Re-Accredited Status for the BSBA programs and Level II First Re-Accredited Status for BS Entrepreneurship in June 2016. 

Furthermore, in 2014, BSBA major in Financial Management was given recognition by the prestigious CFA (Chartered Financial Analyst) Institute. 

Under the leadership of Assoc. Prof. Leonardo M. Canoy, Jr., PhD, the College successfully transitioned to the K-12 curriculum. In compliance with the Commission of Higher Education’s Memorandum No. 18, series of 2017, BSBA major in Human Resource Development Management was changed to BSBA major in Human Resource Management. In 2019, the Bachelor of Science in Entrepreneurship program was granted the Level III reaccredited status by PACUCOA and was awarded the distinction as the First Level III BS Entrepreneurship program in NCR.