Between September 2021 and March 2022, a consortium across the twelve major regions of the UK, led by the Natural History Museum, London (NHM), participated in a study to develop the business case and plan to support a national programme of natural science collections digitisation. This work, funded by the Arts and Humanities Research Council (AHRC) sought to understand the size and diversity of UK natural science collections; establish the readiness of UK institutions to undertake digitisation; and develop training materials to pilot regional digitisation, building on prior investments in digitisation and informatics by the NHM. This report sets out the key findings from this work and is presented as a “blueprint” to scale up digitisation and cooperation through a national infrastructure programme: DiSSCo UK is part of the UK’s contribution to DiSSCo, the Distributed System of Scientific Collections, a partnership of institutions who share a vision to empower science and society, in balance with nature, to make reliable knowledge and evidence about the natural world available to all.