The gardens were established by Sir Thomas Hanbury on a small, steep peninsula jutting southwards from an altitude of 103 meters down into the Mediterranean Sea.

He purchased the extant Palazzo Orengo property in 1867, and over decades created the garden with the aid of pharmacologist Daniel Hanbury (his brother), the botanist and landscape designer Ludwig Winter, and scientists including Gustav Cronemayer, Kurt Dinter, and Alwin Berger.

Initially its care was entrusted to the International Institute of Ligurian Studies but when they withdrew for lack of adequate funds in 1983 responsibility was passed to the University of Genoa.

On 1 June 2006 the Ministero dei Beni e delle Attività Culturali submitted a proposal for the inclusion of the gardens on the list of UNESCO World Heritage Sites.

Major collections include agaves, aloes, and salvia, as well as fine old specimens of Araucaria cunninghamii (planted 1832), Casimiroa edulis (1867), olive trees, Olmediella betschleriana, and Pinus canariensis (1870).