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Istanbul Technical University Faculty of Science and Letters was founded on July 20, 1982 pursuant to the change of the name of Faculty of Fundamental Sciences. On the other hand, Faculty of Fundamental Sciences was established in 1971 by the gathering of the Department of Meteorology and the chairs of the departments lecturing fundamental and general sciences at different faculties at that time. In the academic year of 1971-1972, Meteorological Engineering program started. Then, in the academic year of 1973-1974, Mathematical Engineering program started to accept students and this department produced its first graduates in 1977.

Starting from the academic year of 1977-1978, departments related to economics have been separated from the Faculty of Fundamental Sciences and a new faculty has been established under the name of Faculty of Management Engineering. In the academic year of 1981-1982, Department of Physics Engineering has started to teach. The Department of Meteorology Engineering departed from Faculty of Science and Letters in 1982 and has been admitted to the Faculty of Aeronautics and Astronautics. Six departments of the Faculty of Chemistry, namely Inorganic Chemistry, Organic Chemistry, Analytical Chemistry, Physics Chemistry, Theoretical Chemistry and Coordination Chemistry, have gathered under the Department of Chemistry in the Faculty of Science and Letters.

The Department of Humanities and Social Sciences was founded in 1997 to teach and do research on subjects related to humanities and social sciences.

The Department of Molecular Biology and Genetics was established in 1998 under the name of Department of Biology which had a major emphasis on molecular biology and genetics. In 1999, 22 students enrolled to this program. The Department of Biology has been transformed into the Department of Molecular Biology and Genetics with the approval of the Higher Education Council in January 2000.

The Faculty of Science and Letters currently consists of Departments of Mathematics, Physics Engineering, Chemistry, Humanities and Social Sciences, and Molecular Biology and Genetics.