Approval for a nuclear physics research laboratory at Daresbury was given by the Minister for Science in 1963. The high-energy particle accelerator NINA (Northern Institute's Nuclear Accelerator) was constructed between 1963 and 1965 and first operated in 1966. The Daresbury Nuclear Physics Laboratory officially opened in 1967. Synchrotron Radiation (SR) research began at Daresbury Laboratory in 1968, with the approval of a Synchrotron Radiation Facility (SRF) that made use of radiation from NINA. The SRF was built between 1970 and 1972, and ran until 1977, when NINA closed. The first international symposium for SR users took place at Daresbury Laboratory in 1973 and provided early impetus for the development of the world's first dedicated X-ray SR source.

The second-generation Synchrotron Radiation Source (SRS), a purpose-built storage ring for SR research, was approved in October 1974. The four-year construction project began in April 1975. Construction and commissioning of the linac and booster synchrotron was completed in 1979. Construction of the electron storage ring was completed in 1980. 30 June 1980 saw the circulation of the first beam in the storage ring. Construction of the first two beamlines was completed the same year and on 7 November 1980 the SRS was formally opened by the Minister of State for Science. The first scheduled operation of the SRS for users started in spring 1981, and the electron beam operating current and energy achieved full design specification in March 1982. In November 1982, a 5-tesla superconducting wiggler magnet came into operation to extend the spectrum of X-rays available to higher energies. SR research grew rapidly in the 1980s, and in October 1986 the SRS was shut down for an upgrade to the High Brightness Lattice (HBL). Construction was completed in March 1987.

Following the recommissioning of the storage ring and beamlines in September 1987, attention was focused on improving the quality of the photon beam for users. This involved modernising all beamline photon-position monitoring systems and upgrading the systems used to monitor and control electron beam position. A 6 tesla wiggler unit was installed between November 1991 and June 1992, and came into use in July 1993. In 1997 a share of the Nobel Prize for Chemistry was awarded to Dr. John Walker for research involving data collection at the SRS - this is believed to be the only Nobel Prize to include work on a SR source. A second major rebuilding of the storage ring happened from October to December 1998, when two 2 tesla hybrid permanent magnet multipole wigglers, designed at Daresbury, were installed. Between 2000 and 2004, a further three enhancements to the SRS took place: a protein crystallography facility; a 2.4 tesla hybrid permanent magnet multipole wiggler; and an advanced infra-red beamline. User operation of the SRS ended in August 2008. SR research transferred to the DIAMOND third generation synchrotron facility at the Rutherford Appleton Laboratory in Oxford in 2008.

Daresbury Laboratory continues to operate as a research facility in fields such as accelerator science, bio-medicine, physics, chemistry, materials, engineering and computational science. It is now part of Sci-Tech Daresbury, one of two national science and innovation campuses, which supports scientists, researchers and industry by providing a collaborative and innovative environment to perform cutting-edge research.