The Institute of Plant and Microbial Biology (IPMB) traces its origin to the Institute of Botany, one of the earliest research institutes established by Academia Sinica. Its root dates back to spring 1929, when the National Museum of Natural History, Academia Sinica, was founded in Nanjing, China, comprising two divisions: Zoology and Botany. In autumn 1934, the museum was renamed as the National Institute of Zoology and Botany of Academia Sinica, with Dr. Chia-Chi Wang as the founding director. The Botany Division, led by Dr. Shu-Chun Teng, initially included two research laboratories: the Laboratory of Higher Plants and the Laboratory of Mycology and Plant Pathology. In winter 1936, the Laboratory of Phycology was established to further expand research areas. During the World War II, the institute underwent multiple relocations, moving from Nanjing to Hengyang, then to Yangshuo, and finally to Chongqing. In March 1944, at the Second Annual Meeting of the Second Academia Sinica Council, a resolution was passed to separate the Institute of Zoology and Botany into two independent institutes: the Institute of Zoology and the Institute of Botany. On May 1, 1944, the Institute of Botany was officially established, with Dr. Tsung-Lo Lo as its first director, focusing on Higher Plant Taxonomy and Phycology as the primary research areas. After World War II, it relocated to Shanghai and continued to grow. By 1947, the research areas had expanded to include eight laboratories: (1️) Higher Plant Taxonomy, (2) Mycology, (3) Phycology, (4) Plant Physiology, (5) Forestry, (6) Plant Morphology, (7) Plant Pathology, and (8) Cytogenetics.

In 1949, Academia Sinica was relocated to Taiwan along with the central government. However, most of the institute's researchers remained in mainland China, bringing research activities to a halt. In 1954, under the leadership of President Chia-Hua Chu, Dr. Hsien-Wen Li, a senior researcher of the institute, was invited to lead its reestablishment in Taiwan. The early years were particularly challenging, with no permanent location, a shortage of qualified researchers, and limited research equipment. Dr. Li arranged for newly recruited staff to collaborate with institutions such as the Taiwan Sugar Research Institute and National Taiwan University, making use of their facilities to carry out planned research activities. During this period, the institute's core research focused on rice cytogenetics, led by Dr. Li.

In 1959, the National Council on Science Development (the predecessor of today's National Science and Technology Council) provided funding for Academia Sinica to construct a Biological Research Building on its current Nangang campus. Following its completion in summer 1961, the personnel moved into this new facility, marking the first step towards reestablishing the institute's organizational structure in Taiwan. In 1962, the Institute of Botany was officially reestablished, with Dr. Hsien-Wen Li as the director. The early research focused on rice cytogenetics, radiation-induced mutation breeding, microbiology, and carbohydrate metabolism of bamboo shoots. Operations were supported by funding from the National Council on Science Development, which provided essential resources for equipment, library collections, and research activities. Additional support came through international collaborative projects with the International Atomic Energy Agency (IAEA), the International Rice Research Institute (IRRI), and the United States Department of Agriculture (USDA), fostering the institute's steady growth. Under Dr. Li's leadership, the institute also emphasized talent development. In addition to hosting internationally renowned scholars for summer courses, the institute also sent researchers abroad for advanced training. These training programs contributed to the continuing improvements of this institute.

In 1972, Dr. Hsien-Wen Li retired as director but remained actively involved in research, continuing to mentor and support colleagues. The directorship was succeeded by Dr. Tsong-Teh Kuo. As the number of researchers grew, construction of a new research building began in summer 1974 with support from the National Science Council and was completed in 1975. The building was named as the Hsien-Wen Li Memorial Hall, also known as the institute's South Wing. Upon the building's inauguration, Dr. Li dedicated to the institute his personal motto: “Think more, do more—let science benefit humanity.” This inscription reflects his enduring vision and encouragement for the institute's future.

In 2005, to better reflect the institute's research focus, the name was officially changed from the Institute of Botany to the Institute of Plant and Microbial Biology (IPMB), as approved by the Academia Sinica Council in May. To accommodate the institute's growing space requirements, then-Director Dr. Tuan-Hua Ho successfully secured approval from President Yuan-Tseh Lee for the construction of a new seven-story building on the north side of the IPMB North Wing. Completed in 2009, the Agricultural Technology Building is shared with the Agricultural Biotechnology Research Center and features dedicated spaces for both research and administration, including administrative offices on the first floor, core facilities on the second floor, and IPMB laboratories on the third and fourth floors. A skybridge connects the new and existing buildings, improving spatial efficiency and greatly enhancing the convenience of both research and administrative operations.