Ever since the days of Joseph Henry, some of the more conservative Trustees of the College had questioned the teaching of the secular sciences. It was not until McCosh's administration that the study of the various branches of science formed an important component of the academic offerings of the College.

McCosh proposed the construction of a School of Science at the December 1871 meeting of the Board of Trustees. By the following winter the foundation had been laid for a three-story structure devoted entirely to science classrooms and laboratories. Named the John C. Green School of Science in honor of its principal benefactor, the building was designed by William A. Potter in the High Victorian Gothic style. Years later, when this style fell into disfavor upon the rise of the Collegiate Gothic style, the virtues of such buildings often went unappreciated. (The Princeton Herald once called the School of Science "a perfect example of the most decadent period of American architecture.") In fact, the School of Science was entirely appropriate at the time it was built, from both stylistic and academic perspectives.

Located near the corner of Nassau Street and Washington Road, the School of Science anchored the eastern end of the front campus. It was a U-shaped building, and its main facade faced to the west, toward the new and similarly styled Chancellor Green Library.