Thanks to the initiative of Władysław Szafer, an outstanding scholar and Professor of the Jagiellonian University, on October 5, 1953, the Scientific Secretariat of the Polish Academy of Sciences (PAS) established the Department of Botany as an independent, national scientific institution located in Kraków. The Department of Botany was upgraded to the Institute of Botany on April 5, 1956. On June 10, 1986, according to the decision of the Scientific Secretariat of the Polish Academy of Sciences, the Institute's name was changed to the “Władysław Szafer Institute of Botany.”

The Institute was established in Krakow, the city with a long tradition of physiographic botanic experiments which had been performed at the Physiographic Committee of the Polish Academy of Arts and Sciences for more than 100 years. The Institute's intellectual and scientific foundations were established on the basis of more than 40 years of activity at the Department of Systematics and Geography of Plants of the Jagiellonian University. During the initial years of activities at this new botanical institute, the scientific program incorporated many recommendations and ideas of Prof. Marian Raciborski (the first head of the Department in 1912–1917).

The first employees of the Department of Botany of the Polish Academy of Sciences, consisted exclusively of the personnel of the Department of Systematics and Geography of Plants, Jagiellonian University, who were full-time employees of the University and part-time (50% time) employees of the Institute. Only the Director of the Institute (Prof. W. Szafer) and the Deputy Director (Prof. B. Pawłowski) were full-time employees of both, the Institute and the University. In 1953 the Polish Academy of Arts and Sciences assigned the large Herbarium of Polish Flora to the Polish Academy of Sciences and the curator of the Herbarium also became a full-time employee of the Institute.

Prof. Szafer wished to establish in Krakow a prominent research center specializing in systematics and geography of plants as well as paleobotany. These three disciplines have been the major research areas of the Institute since its establishment. The directions of the Institute's scientific activities outlined in 1953 by Prof. Szafer have been carefully followed and developed and new disciplines have also been studied, such as the variability of plants, ecology, algology, and in recent years, environmental ecology, ecological monitoring, bioindication and paleoethnobotany. Some of the traditional scientific disciplines initiated by Prof. Szafer changed their names to more modern terms such as biosystematics, palynotaxonomy, and paleoecology.

In 1954 the Department of Botany of the Polish Academy of Sciences had only three laboratories: Polish Flora (vascular plants), Bryology, and Paleobotany which consisted of 30 employees (including administration and support services). After receiving a higher employment quota from the Polish Academy of Sciences in May 1954, the Institute began to develop dynamically. New laboratories were established such as the Atlas of Polish Flora (located in Wroclaw), Algology, Variability and Historical Evolution of Plants, and later the Laboratories of Mycology and Lichenology. The number of employees increased every year and reached relative stability in the beginning of 1960's (72–74 employees). In 1961 the Institute was critically affected: the Ministry of Science and Higher Education issued new regulations that did not allow the academic faculty to have a joint appointment in the Polish Academy of Sciences. By the end of 1962, when most of the members of the Jagiellonian University’s faculty had already left the Institute, 58 persons remained in the Institute's staff. However, the number of employees continued to grow rapidly and reached 107 in 1970. During the next 20 years the number of employees varied, reaching the lowest number of 107 in 1970 and 1990, and the highest-numbers of 131 and 130 employees in 1974 and 1980, respectively. Because of the reduced financial support for science in Poland in 1988–1991 the number of employees consistently decreased. In 1992 the employment quota for the Institute was reduced by 18 positions to the current level of 86. From the 1993 the number of employees continued to grow up to 93 people. Currently (end of February 2011), 91 people work at the Institute, 9 professors, 5 ass. prof., 28 adjuncts, 1assistants, 17 technicians, 5 librarians, and 22 people in the administration and support.

In addition to these personnel changes, the character of the research activities simultaneously changed as well, such as a continuously broadened research scope. Later, during a period of higher stability (1970's and 1980's) the Institute coordinated the multi-departmental basic programs and participated in the research coordinated by other institutions. Currently, 72 research projects within 11 topic groups are in progress.

Although the Institute has focused on basic research, applied research has also been an integral part of the Institute's mission. During the entire 40 years of its existence the Institute's role to serve society's needs has been strongly emphasized. In 1961 W. Szafer wrote: “the Institute of Botany has not only solved problems related to the development of botany for the country, but it has also participated in solving problems from other disciplines of science. This example proves that the Institute of Botany fulfills the current needs presented by the society. By achieving these tasks, often in the form of expert reports, the Institute of Botany actively participates in the life of the entire nation.”

During the first year of its existence the Department of Botany of the Polish Academy of Sciences implemented the program “Plant Communities as a Basis for Economical Planning.” Effects of fertilization on development of the meadows of the Tatra Mountains, characterization of plant communities of the planned Goczalkowice retention reservoir and research on algae polluting drinking water were among the research topics of that programme.

Another programme “Botany Serving Society,” included activities such as: re-cultivation of the cinder tips in Upper Silesia, the Lubin Copper Basin, the Tarnobrzeg Sulphur Basin; paleobotanical studies for the geological service needed for planning spatial development of the country; and organization of lectures encouraging people to participate in activities in natural settings. The Institute also organized exhibitions of edible and poisonous mushrooms, prepared open-houses for schools, etc.

In addition, the Institute established various culture-support activities in the areas of archeobotany, prehistory, and history (paleobotanic studies of the excavations in the Krakow Market Square and the Wawel Castle). Recently the Institute has started a wide range of studies on environmental pollution, including biological monitoring in Krakow, evaluation of effects of heavy metals from vegetables grown in allotment plots on human health, and cooperation of palinologists with the medical personnel of the allergy clinics.

Initially, the newly developed Institute of Botany of the Polish Academy of Sciences and the Department of Systematics and Geography of Plants of the Jagiellonian University were located in the old, two-story building at 46 Lubicz Street. Because of the need for more space, in 1954 the new three-story building adjacent to the old building was finished which housed the Institute's laboratories. The herbarium belonging to the University and the Academy of Sciences was located on the first floor and the library on the second floor of this new building.

During 1961–62 the old building of the Department was remodelled and the third floor that housed the Department of Paleobotany was added. In 1961, in the large hall of that floor an exhibition of the sixth INQUA Congress was displayed; currently the Museum of Paleobotany is located there. Construction in 1966 of a modern, five-story building in the backyard of 46 Lubicz Street was the last phase of the Institute's development.

In years 1999-2012 the whole herbarium of vascular plants and cryptogames was modernized and the laboratories were rebuilt. The building at the front was extended and its top floor was occupied by laboratories (Molecular Analysis Laboratory). A new Library building was built as well together with a reading room and storage rooms.

A Molecular Analysis Laboratory and Educational Centre of Natural Sciences ere founded in 2011.

Prof. Władysław Szafer  (paleobotanist and taxonomist opf vascular plants) was the director of the Institute in 1953–1960, Prof. Bogumił Pawłowski (taxonomist, fitogeograph  of vascular plants) in 1961–1968, Prof. Adam Jasiewicz (taxonomist of  vascular plants) in 1969–1983, Prof. Kazimierz Zarzycki (ecologist)  in 1984–1990, Prof. Leon Stuchlik (paleobotanist) in 1991-1999 and prof Zbigniew Mirek - (taxonomist of vascular plants)  in 1999-2011. Currently, the function is performed by prof. Konrad Wołowski (phycologist) 2011-.