The ceremonial opening of the Academy of Sciences was held in Minsk on January 1, 1929, on the tenth anniversary of the Belarusian SSR. The first president of the Academy of Sciences was historian Professor V.M. Ignatovsky.
On the opening day, the staff of the Academy of Sciences consisted of only 128 people, including 87 research workers. However, from the very beginning, the Academy of Sciences has become a leading scientific center influencing the economic, technological, social and cultural development of Belarus. By the beginning of 1941, about 750 people worked at the Academy of Sciences. In its structure there were 12 research institutions, of which 9 institutes.
During the Great Patriotic War (1941-1945), the normal activities of the Academy of Sciences were interrupted. Some scientists continued their research in the institutes of Russia and other regions of the former Soviet Union. Many members of the Academy of Sciences took part in the hostilities against the Nazi invaders.
During the war years, the Academy of Sciences, as well as the entire national economy of Belarus, suffered enormous damage. Scientific laboratories, equipment, buildings, library funds were burned or looted. In 1945, the total number of employees of the Academy of Sciences was 360 people.
After the liberation of Minsk in July 1944, by the beginning of 1945, eight academic institutes resumed their activities, and in 1951 there were already 29 scientific research institutions in the Academy of Sciences, 16 of which were institutes. The total number of employees reached 1234 people, 33 academicians, 27 corresponding members, 55 professors and doctors of science, 165 candidates of science worked in the Academy of Sciences.

The profile of further research works of the Academy of Sciences was shaped by the changes in the structure of the national economy of the republic, the needs for the development of science, established traditions and existing scientific potential. The development of the Academy of Sciences and the training of specialists for its institutes were carried out with the support of the governments of Belarus and the USSR, as well as the leading scientific centers of Moscow, Leningrad and other cities of the former Soviet Union.
In 1997, in accordance with the Decree of the President of the Republic of Belarus of May 15, 1997 No. 281 "On the National Academy of Sciences of Belarus", the Academy of Sciences was transformed into the National Academy of Sciences with the status of the highest state scientific organization of Belarus, responsible for coordinating and conducting basic scientific research.

In order to strengthen the status and increase responsibility for the development of science by the Decree of the President of the Republic of Belarus of March 5, 2002 No. 7, the NAS of Belarus was entrusted with the functions of the republican government body on some issues of financing scientific and innovative activities, developing informatization and the system of scientific and technical information, monitoring for the effective use of public funds allocated to finance research and development, as well as scientific and technical expertises. To effectively solve the tasks facing the National Academy of Sciences of Belarus, it included the Academy of Agrarian Sciences of the Republic of Belarus, the Belarusian Republican Foundation for Basic Research, the Belarusian State Research and Production Concern of Interindustry Machine Building and Instrumentation, the Belarus State Research and Production Concern of Powder Metallurgy, and other organizational structures.