In the first half of the nineteenth century, the Liverpool Botanic Garden was an important centre for the cultivation of plants from all over the world sourced from pioneer explorers. In this paper the history of the Garden from its foundation in 1802 to 1858 is discussed; a brief overview of its subsequent fortunes is also given. Critical to the workings of the gardens were its first two curators, John and Henry Shepherd, and three assistant gardeners, William Harrison, William Skellon and James Shillito. Hitherto, little has been written on these individuals, especially the latter three. Accordingly, a substantive appendix is included, giving detailed comments as to their lives and careers both before and during their time with the Liverpool Botanic Garden. Whilst much primary data pertaining to the Garden has been lost over the years, this paper draws together existing knowledge and newly discovered sources to demonstrate the scientific and horticultural significance of the Garden.