The former Gothic building that housed the school from its founding in 1938 to 1959
The Bronx High School of Science was founded in 1938 as a specialized science and math high school for boys, by resolution of the Board of Education of the City of New York, with Morris Meister as the first principal of the school. They were given use of an antiquated Gothic-gargoyled edifice located at Creston Avenue and 184th Street, in the Fordham Road-Grand Concourse area of the Bronx. The building, built in 1918 for Evander Childs High School, had been successively occupied by Walton High School (1930) and by an annex of DeWitt Clinton High School (1935). The initial faculty were composed in part by a contingent from Stuyvesant High School.[22]
Principal Meister put his imprint on the school from its formation, for example selecting as school colors "green to represent chlorophyll and gold the sun, both of which are essential to the chain of life."
 
Expansion to co-education
Bronx Science started with about 150 ninth year students and 250 tenth year students, the remaining facilities of the building being used by DeWitt Clinton. As more boys began to attend Science, the Clinton contingent was gradually returned to its own main building. During their joint occupation, which lasted for 2 years until 1940, the two schools had separate teaching staff and classes, but the same supervision and administration.
In 1946, as a result of the efforts of Meister, the faculty, and the Parents Association, the school became co-ed, giving girls of New York equal opportunity to pursue a quality education in a specialized high school, previously denied to them. This expansion to co-education preceded its rivals Stuyvesant (1969) and Brooklyn Tech (1970) by more than two decades.
In 1958, after 20 years as principal of the school, Morris Meister resigned to become the first president of the newly organized Bronx Community College. Alexander Taffel succeeded Meister as principal.
 
Recent administration
When Alexander Taffel retired as principal in 1978, the chairman of the Biological Science Department, Milton Kopelman, became Principal.[25] He remained so for over ten years. Upon Principal Kopelman's retirement in 1990, long-time faculty member and Biology Assistant Principal Vincent Galasso became principal. He was followed by Physical Science Department Assistant Principal Stanley Blumenstein, a 1963 graduate of Bronx Science.
In 2000 William Stark, an assistant principal of the Social Studies Department, was appointed acting principal. He was expected to move up to the principal's office, when Chancellor Harold O. Levy decided to try to find a Nobel laureate to become principal.[26] However, when that effort failed, Stark was still not offered the job as principal. Stark said that if he wasn't officially offered the job by a certain date, he would take another position being offered to him elsewhere. When the deadline came and went, Stark accepted a job as principal of Manhasset High School. Many faculty and parents were upset that Stark was not appointed in a timely way and thus had left the school; Vincent Galasso agreed to an interim appointment for one term in 2001.
 
After Levy's unsuccessful attempt to appoint a Nobel laureate, Valerie J. Reidy, Assistant Principal of the Biology Department, was appointed principal in September 2001; she was the first female principal in the school's history. Reidy has been a controversial figure, and several teachers[who?] left the school in response to her becoming principal. Some teachers[who?] have openly criticized her to newspapers and some students staged protests in 2005 and 2008.[26][27][28] There was also a substantial exodus of social studies teachers at the end of the 2010–2011 term, reportedly due to problems with the administration.