In 1955, the Nuclear Physics Institute of the Czechoslovak Academy of Sciences was founded at Řež as a basic Czechoslovak institution in the nuclear fields. Lately, the institute was renamed as the Nuclear Research Institute CSAS.

The nuclear power industry development led to the separation of the institute into several parts in 1972. The largest part, devoted mainly to the applied research, was subsided to the Czechoslovak Commission for Atomic Energy under the name Nuclear Research Institute. In 1992, this institute was privatized to Nuclear Research Institute Řež plc.

The second largest part, devoted mainly to the basic research, remains a part of the Czechoslovak Academy of Sciences under the name Nuclear Physics Institute CSAS. In 1979, the Low-Temperature Department passed from NPI to the Institute of Physics CSAS. In 1993, NPI became one of the institutes of Czech Academy of Sciences. Former Institute of Radiation Dosimetry CAS in Prague was connected to NPI as a detached branch in 1994. The Laboratory of Neutron Activation Analysis passed from Czech Environmental Institute to NPI in the same year. Since 2007, the institute is a public research institution.

At the present time, Nuclear Physics Institute of the CAS, public research institution, is involved essentially in the experimental and theoretical nuclear physics, including the intermediate-energy physics and the heavy-ion physics at the interface of nuclear and subnuclear physics. Research in a wide range of related fields like solid state and material research by neutron scattering, theoretical physics of elementary particles and mathematical physics, dosimetry of ionizing radiation is also performed. Applied research is performed at NPI, especially with the help of nuclear analytical methods, i.e., the elemental analysis by pattern irradiation by charged particles or neutrons. Nuclear analytical methods are used in the interdisciplinary research as material research, ecology, archaeology etc. The research and development of radiopharmaceuticals is performed, the radiopharmaceuticals production was transferred to the daughter company RadioMedic ltd. in 2009, NPI being its only associate. ÚJV Řež a.s. is the new owner of the RadioMedic company since 2023.

The most important experimental facilities of the institute are isochronous cyclotron U-120M, fast neutron generator based on it, new cycloctron TR-24, tandem electrostatic accelerator Tandetron 4130 MC installed in 2005 with facilities for various nuclear analytical methods, equipments for neutron diffraction and scattering used mainly in the material research and installed at the nuclear reactor LVR-15 operated by Research Centre Řež (CVŘ). The domestic experiments are in equilibrium with the participation at large international experiments as ALICE at CERN.