In July 1980, during the 14th Convocation of Academicians of Academia Sinica, a group of twenty-one academicians, including Academicians Yuan-Shih Chow, George C. Tiao and Ching Chun Li, drafted a resolution calling for the establishment of the Institute of Statistics. On July 1, 1982, the Preparatory Office was founded with Dr. Min-Te Chao as the Director. Five years later, the Institute of Statistical Science was formally founded on August 3, 1987, and Dr. Chao was the Founding Director from 1987 to 1993. The successive Directors were Dr. Ching-Zong Wei (August 1993-August 1999), Dr. Chen-Hsin Chen (August 1999- December 2002), Dr. Ching-Shui Cheng (January 2003-December 2005), Dr. Gwo Dong Lin (Acting Director, January - June 2006), Dr. Ker-Chau Li (July 2006 - July 2012), and Dr. Chen-Hsin Chen (Acting Director, July 2012 - July 2013), Dr. Ching-Shui Cheng (July 2013 - June 2016), and Dr. Jeng-Min Chiou (Acting Director, July 2016 - July 2017), and Dr. Chun-houh Chen (Director, July 2017 - July 2023). Dr. Hsin-Chou Yang has been the Director since July 2023.

The Institute of Statistical Science conducts fundamental and applied research related to statistics and probability. The Institute respects independent research of individual principal investigators, encourages team work of research groups, and promotes multidisciplinary collaborations and cross-institution research projects. Major research areas include probability and its applications, mathematical statistics, bioinformatics, medical and genetic statistics, brain imaging analysis, time series, spatial and environmental statistics, experimental design, statistical machine learning, statistical graphics, data visualization, smart health, precision medicine, network analysis, deep learning, and artificial intelligence. The Institute currently has 32 research fellows, 21 postdoctoral fellows, 48 research assistants, and approximately 21 supporting staff members in administration and computing.

Research fellows in the institute have published research work in reputable international journals and books and are actively involved in the organization and participation in international conferences. In the past 3 years, researchers of the institute have published 326 articles in SCI journals. The international journal, Statistica Sinica, published by the institute has become one of the major statistical journals in the world.