The Qiushi Academy was chartered in 1897. This was the original name of Zhejiang University, which was one of China's earliest modern higher education institutes. In the beginning, the Academy offered lectures on arithmetic, physics (known as Gezhi then) and chemistry. It also set up a physics instrument laboratory and a chemistry laboratory. In 1928 the Qiushi Academy was officially renamed as Zhejiang University. The College of Art and Science was created in August that year with Shao Peizi as its first dean. The college had the following science departments (known as courses then): mathematics, physics, chemistry, and psychology. The Department of Psychology was discontinued in 1930. By 1936 when the renowned meteorologist and educator Zhu Kezhen (also known as Chu K'o-chen or Co-ching Chu) became President of Zhejiang University, the College of Art and Science composed seven departments: foreign languages, education, history & geography, mathematics, physics, chemistry and biology. Distinguished professors at the College included Chen Jiangong (Kien-Kwong Chen), Su Buqing (Bu-Chin Su), Zhang Shaozhong, Bei Shizhang (Shitsan Pai), Zhou Houfu, and Shu Xingbei (Hsin Pei Soh). Invited by President Zhu, physicists Hu Gangfu (Kang-fuh Hu) and Wang Ganchang (Kan Chang Wang), and chemist Wang Jin, among others, joined Zhejiang University. With the talented scientists, the science departments prospered. In 1939 the College of Art and Science split and Hu Gangfu became dean for the College of Science. The College of Science then had the departments of mathematics, physics, chemistry, and psychology, as well as the Mathematical Research Institute and the Biological Research Institute. 

In 1937, the War of Resistance Against Japan broke out. Led by President Zhu, the professors and students of the College of Science moved together with the university to the southwest of China and spent nine remarkable years there. During the period, the professors and students continued to teach, learn, and conduct research under harsh conditions. A number of remarkable scientific achievements were made then, e.g., by Su Buqing on differential geometry, by Chen Jiangong on trignometric functions, by Wang Ganchang on neutrino, by Shu Xingbei on the theory of relativity, by Zhou Houfu on atomic theory, by Bei Shizhang on sex plasmid and sex inheritance, and by Chen Li on intelligence test and personality test. Meanwhile, the College of Science at Zhejiang University cultivated a large number of outstanding students such as T. D. Lee, Cheng Kaijia, Ye Duzheng, Gu Chaohao, and Hu Jimin. It had gained better and better reputation. In 1944, Joseph Needham, fellow of the Royal Society and biologist at the University of Cambridge, visited Zhejiang University twice. After visiting the College of Science in Meitan, Guizhou, he praised the university as the Oriental Cambridge. In 1946, Zhejiang University moved back to east. By March 1948, the College had five departments (mathematics, physics, chemistry, biology, and pharmacy) and four research institutes (mathematics, physics, chemistry, and biology).

In the nationwide restructure of higher education in 1952, the main part of the College of Science joined Fudan University in Shanghai and the rest was transformed to the Zhejiang Normal College. In 1958, Zhejiang Normal College merged into the newly founded Hangzhou University. Thereafter, the science deparments were reestablished separately in Zhejiang University and in Hangzhou University. After evolution in the following half century, the science departments in the two universities, which shared the same root, had made significant progress.

In September 1998, approved by the Ministry of Education of China and the government of Zhejiang Province, Zhejiang University, Hangzhou University, Zhejiang Agricultural University, and Zhejiang Medical University were merged to form the new Zhejiang University. In July 1999, the new College of Science was established and He Xiantu, member of the Chinese Academy of Sciences, became head of the College. He proposed the slogan of Reviving the Science Education of Zhejiang University. With rapid development in the following ten years, the College stepped up to a new level in scientific research, scientist training, and team building.

In 2008, Zhejiang University reformed its faculty system. The College of Science was transformed into the Faculty of Science in June 2009. Inheriting the spirit of Seeking the truth and being innovative, the members of the Faculty devoted to revitalizing the science education at Zhejiang University, making further progress.