The National Railway Museum (NRM) was opened at Leeman Road in York in 1975. The 1968 Transport Act prompted British Railways (BR) to work with the Science Museum to develop a National Railway Museum to house BR's collection which was held at the Museum of British Transport in Clapham. The NRM's holdings also derived from the railway collections held by the Science Museum and the former York (Queen Street) Railway Museum.

The NRM's mission is aligned with the Science Museum Group (SMG)'s core strategic priorities to 'Grow ‘science capital’ in individuals and society... Grow our audiences and exceed their expectations... Sustain and grow our world-class collection.' The museum holds the ‘The National Collection of historical railway relics’, Britain’s largest single body of historic railway items to allow audiences to '...explore the huge impact of railways on Britain and the wider world.' It was the first national museum to be located outside London and has won European Museum of the Year on two occasions in 1990 and 2001.

The NRM is integrated into the SMG's governance structure and has an Advisory Board that advises the NRM's Director and the Board of Trustees of the Science Museum on its cultural offer. The NRM's first Director was Dr John Coiley, who served from 1974 to 1992, subsequently Andrew Dow, Andrew Scott, Steve Davies, Paul Kirkman and Judith McNicol have held the post.

The museum site has been extended on several occasions. In 1990, the Station Hall and the Peter Allen Building opened across Leeman Road in York’s former railway goods depot. The Great Hall underwent major structural works between 1990 and 1992. The former diesel depot adjacent to the Great Hall was added as a store and in 1999 this was rebuilt to become The Works, providing public access to collections stores, workshops and a viewing gallery overlooking York Station. From the 1980s onwards the NRM had a collections store at Foundry Lane in York, this closed in 2011 when the SMG opened a collections store at Wroughton, near Swindon. The site at Wroughton continues to function as the NRM's deep storage facility and is now known as the National Collections Centre.

The NRM has developed its academic credentials and research facilities over time. The Institute of Railway Studies was launched in 1994 as a joint venture between the NRM and the University of York. In June 2004, the Yorkshire Rail Academy was opened – a joint development between York College and the NRM to train rail engineering apprentices, it closed in 2014 after a rail industry partner, Viva Rail, ceased trading. The NRM's research centre, Search Engine, opened in 2008 with assistance from the Heritage Lottery Fund and the Higher Education Funding Council to provide enhanced access to the NRM's archive and library collections.

In 2004 Locomotion: the NRM at Shildon, County Durham, opened as a joint venture with local authority partners to preserve Shildon's railway heritage and display rail vehicles from the National Collection. The site includes historic structures associated with the Stockton & Darlington Railway and buildings that made up Shildon's earlier Timothy Hackworth Museum.