The Institute of Chemistry and Cell Biology (ICCB) was established at Harvard Medical School in 1998, by Co-Directors Dr. Stuart Schreiber and Dr. Timothy Mitchison, to facilitate the pursuit of Chemical Genetics as an academic discipline. At the time, techniques for high-throughput screening of small molecule libraries in biological assays were being developed in the biotechnology and pharmaceutical industries as a means to speed the identification of lead compounds for drug discovery. ICCB was one of the first high-throughput screening facilities to be opened in an academic setting.

In 2002, Dr. Schreiber and the ICCB were awarded an Initiative for Chemical Genetics (ICG) contract from the National Cancer Institute, and the ICCB became known as the ICCB-ICG. The high-throughput screening facility was a central component of the ICCB-ICG. 

In 2003, Harvard Medical School, as part of a regional consortium, was awarded a program grant from NIAID to establish the New England Regional Center of Excellence in Biodefence and Emerging Infectious Diseases (NERCE/BEID). ICCB-Longwood participated as part of the NERCE Center, hosting the National Screening Laboratory for the Regional Centers of Excellence for Biodefence and Emerging Infectious Diseases (NSRB). The NSRB and NERCE program were active at Harvard Medical School through March 2014. 

In April 2005, ICCB-ICG evolved into two groups: the Broad Institute Chemical Biology Program (BCBP), located at the Broad Institute of Harvard and MIT, and ICCB-Longwood, located at Harvard Medical School. The ICCB-Longwood Screening Facility remains in the location previously occupied by the ICCB at Harvard Medical School. ICCB-Longwood serves primarily Harvard Medical School and Harvard-affiliated hospital researchers.

The ICCB-Longwood Investigator Initiated Screening Program assists academic researchers in carrying out high-throughput screens of chemical and RNAi libraries to identify new tools for biological research. The facility employs a staff-assisted screening model, in which investigators using the facility are provided access to compound and siRNA libraries, and training in the use of some instruments, such as liquid handling equipment, plate readers, and screening microscopes. Staff members handle all library plates and run the complex automation for screens.