The College of Agriculture and Food Science can trace its roots in as early as 1907. The then Acting Director of the Philippine Bureau of Education assigned Dr. Edwin B. Copeland of the Philippine Normal School to select a site for an agricultural school. Dr. Copeland recommended Los Baños at the foot of Mt. Makiling in Laguna. The Bureau of Education approved the site and appointed Dr. Copeland as the Superintendent of the School of Agriculture. In 1908, the Governor General at that time signed Act No. 1170 creating the University of the Philippines. Act No. 1870 required a minimum of three colleges in operation for the establishment of the University in which the College of Agriculture was one of the three thus establishing the College on March 6, 1909. On June 14 of the same year, the College of Agriculture opened its doors to its first 12 students.

The first building of the College called the “temporary building” was inaugurated in 1910. As other buildings rose on the campus, it became known as the old “College building”. At this time, the Department of Agronomy was established with Dean E.B. Copeland as its first chairman and the Department of Agricultural Chemistry was also founded with Dr. Horace G. Deming as its first chairman.

In 1911, the journal Philippine Agriculturist and Forester was founded and published monthly by the student body of the College with Mr. Manuel L. Roxas as its first editor. The following year, the Department of Agricultural Engineering was organized and Professor Albert G. Glodt served as its first chairman. Succeeding these, in 1913, the Graduate Studies became available in the College.  On the other hand, the Department of Plant Pathology was created in 1917 with Professor Otto A. Reinking as its first head. Subsequently, in 1918, the Philippine Agriculturist and Forester was renamed Philippine Agriculturist. On the same year, the Agricultural Experiment Station which was later renames as the Central Experiment Station was fully established on 15 February by virtue of Act. No. 2730 of the Philippine Legislature. Through this, the College was able to acquire a large tract of land aggregating about 260 hectares for the development of its experimental works. The Division of Rural Economics which was later renamed to Department of Agricultural Economics on the other hand started in 1919 with Mr. Evett B. Hester as its first chairman.

Loyalty Day in UPLB was first celebrated at the Botany Building presently the Biological Science Building. On 22 January 1922, The Board of Regents (BOR) of the University approved a resolution from the student body to make a Loyalty Day an annual celebration in the College. This 2018, Loyalty Day will celebrate its 100 years.

The Department of Animal Husbandry chaired by Dr. Bienvenido M. Gonzales was established in 1923. Before its establishment, Professor Sam B. Durham was already offering a single course in Animal Husbandry to a few pioneering students of UPCA. Meanwhile, the Department of Plant Physiology opened its doors in 1925 with Dr. Gerardo O. Ocfemia as its first chairman. Dr. Ocfemia would later be recognized as the “Father of Plant Pathology” in the Philippines. The Green and Gold Magazine, a supplement of the Philippine Agriculturist was launched with its colors symbolic of the “green of life and spring, and the gold harvest and fulfillment” and presented digests of foreign agricultural works and the results of students’ theses.

In 1928, as the need for teachers became apparent and by virtue of the Philippine Legislature Act 3377 known as the National Vocational Education Act No. 1927, the Department of Agriculture Education was established in March 1928 by the BOR of the University of the Philippines. Under the same department, the University of the Philippines Rural High School was also established in 1929 to serve as training laboratory for observation and practice of teaching students enrolled in the teacher training program and an experiment school for secondary education in agriculture. Dr. Merle A. Foster acted as its first department chairman and high school principal.

The Department of Soils which was formerly under the Division of Agronomy was founded in 1930 wherein Dr. Robert I. Pendleton was its first chairman. Seven years after, in 1937, the Department of Plant Physiology was renamed the Department of Agricultural Botany. The College did not stop growing and in 26th of October 1950, the UP BOR established the Graduate School which was headed by the Dean of the College of Agriculture. Further, under the College, the Department of Home Technology was established in 1951. The extension program of the College also flourished and on 2 June 1959, the Agricultural Credit and Cooperative Institute (ACCI) opened its doors under the Department of Agricultural Economics. The College of Agriculture continued to develop and on 1st of November 1962, the Dairy Training Research Institute (DTRI) was organized through a Memorandum of Agreement between UPLB and the Department of Agricultural and Natural Resources with Dr. Gonzalo V. Garcia as its first Director.

As a premier institute of Agriculture in the country, the College was chosen to be the host institution of the Southeast Asia Regional Center for Graduate Study and Research in Agriculture (SEARCA). The then Dean of the College, Dr. Dioscoro L. Umali became its first director. Moreover, the College expanded in La Granja, La Carlota City, Negros Occidental when the La Granja Research and Training Station (LGTRS) was opened through Republic Act 2415 on 21st of June 1959. The station is maintained for research, training and extension in the production, processing, utilization and marketing of sugarcane and selected crops and livestock.

As the College expanded in the 1970s, on 29 June 1972, the Department of Soil Science was approved by the BOR to replace the Department of Soils. Few days after, on 1 July 1972, formerly a division under the Department of Chemistry, the Division of Food Science & Technology (DFST) was officially created upon the decision of the UP BOR with Dr. Ricardo R. del Rosario as its first chairman. Presidential Decree No. 58 on 20 November 1972 elevated the UP Los Baños to university status giving UPLB greater autonomy in academic, administrative and fiscal matters. The College became the core of UPLB, together with the College of Forestry, Graduate School, ACCI, Agrarian Reform Institute (ARI) and the DTRI. A month after, on 21 December, the UPLB Graduate School became a separate unit from the College. On 28 March 1974, upon the decision of the UP BOR, the Department of Horticulture was created and Dr. Eduardo C. Quisumbing served as its first chairman. In 1975, through Presidential Decree 729, the Institute of Plant Breeding (IPB) was established and Dr. Emil Q. Javier acted as its founding director. The institute research thrusts cover all crops except rice.  Another research institute, the National Crop Protection Center was established on 21 May 1976 by virtue of Presidential Decree No. 936 with Dr. Fernando C. Sanchez acting as its first director. Research in the College was thriving at that time and on 27 October 1977, the Australian government through the Association of Southeast Asian Nations (ASEAN) – Australia Economic Cooperation Program presented to UPLB the Postharvest Horticulture Training and Research Center (PHTRC) during the 9th Ministerial Meeting of the member countries of the ASEAN. With all of the efforts of the College to extend assistance to the community, on 31 August 1977, the Ramon Magsaysay Award for International Understanding, a prestigious award given to individuals or organizations for their valuable contributions to the advancement of friendship, tolerance, peace, and solidarity as the foundations for sustainable development within and across countries was granted to the College of Agriculture.

As the College grew, it units also grew with it. In 1982, the Institute of Food Science and Technology, the Institute of Animal Science, and the Farming Systems and Soils Resources Research Institute (FSSRI) were established on 16 October by virtue of Executive Order No. 840 as part of the National Agriculture and Life Science Research Complex. Meanwhile, the Department of Agricultural Education and Rural Studies was also established from the Department of Agricultural Education with Dr. Leonardo A. Chua as its first chair.  Also, one of the major changes was in 1998, the Philippine Agriculturist was renamed the Philippine Agricultural Scientist (PAS) to reflect the change in focus in the last decade from technologies to technological studies and laboratory experiments. On 1 June 2002 from the Department of Agricultural Education and Rural Studies, the Department of Soil Science and the Farming Systems and Soil Resources Research Institute, the Agricultural Systems Cluster was established with Dr. Eduardo P. Paningbatan Jr. as the first director.

A big College, on 30 January 2003, the UP BOR during its 1167th meeting approved the reorganization of the College of Agriculture into five functional clusters namely: Agricultural Systems Cluster (ASC), Crop Science Cluster (CSC), Crop Protection Cluster (CPC), Animal and Dairy Sciences Cluster (ADSC), and Food Science Cluster (FSC). The UP Rural High School was also transferred to the College of Arts and Sciences (CAS) in the same year. On 14 December 2006, the CA Agripark was launched to serve as a one-stop shop for agricultural products, technologies, publications and technical services in agriculture. Then came 2007, the UPLB CA was recognized by the Commission on Higher Education (CHED) as Center of Excellence (COE) in Agriculture Education. Since then, the College has been a regular recipient of this award. Aside from this, the College is also the consistent top performing school in Agriculture Licensure Examination since the licensure exam has been administered.

After 13 years, the College once again underwent restructuring and on 16 December 2016, during the 1323rd meeting of the UP BOR, the College was renamed from College of Agriculture to College of Agriculture and Food Science (CAFS). The aim of restructuring is to realign the units of the College to their respective relevant agribusiness subsectors in agriculture. From five clusters, five degree-granting institutes and four research and training institutes composed the new CAFS.

Currently, the College continues to improve the quality of its program. Part of it was the accreditation of BS Agriculture Program to the ASEAN University Network – Quality Assurance (AUN-QA) last 16 March 2017. Other degree programs of the College are already lined up for the assessment to ensure that quality assurance of the College are in place.