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. Meister personally selected a teacher, Alexander Taffel, to succeed him as principal.

The initial faculty were composed in part by a contingent from Stuyvesant High School.

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." Bronx Science started with about 150 ninth year students and 250 tenth year students, the remaining facilities of the building being used by De Witt Clinton.

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 De Witt Clinton High School (1935).

Each November, about 30,000 eighth and ninth graders take the 3-hour test for admittance to eight of the nine specialized high schools.

Approximately 1,000 to 1,050 applicants are accepted each year.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.The main lobby entrance featured a 63-foot (19 m), Venetian glass mosaic mural overhead, depicting major figures from the history of science such as Marie Curie and Charles Darwin under the protective hands of a God-like figure representing knowledge, with this quote from John Dewey: "Every great advance in science has issued from a new audacity of imagination." The mural is an original work by Frank J.Reilly entitled Humanities Protecting Biology, Physics, Chemistry.When Alexander Taffel retired as principal in 1978, the chairman of the Biological Science Department, Milton Kopelman, became Principal. Upon Principal Kopelman's retirement in 1990, long-time faculty member and Biology Assistant Principal Vincent Galasso became principal.