Giovanni Panerai (1825–1897) opened up his first watch shop in Florence, Italy in 1860. Giovanni’s grandson Guido Panerai (1873–1934) expanded the watch shop “Orologeria Svizzera” and took over his wife’s family business, a mechanical workshop. In 1915, Guido Panerai invented gun sights that were illuminated by a radium-226/zinc sulfide powder enclosed in small, hermetically sealed vessels. Radiomir, the name for the radium-based luminous mixture is derived from “radio mire”, which is Italian for “radium sights”. Panerai became an official supplier to the Regia Marina (the Royal Italian Navy), supplying a variety of technical equipment and precision instruments. All Panerai watches, except for the GPF 2/56 were designed and manufactured by Rolex SA using pocket watch movements made by Swiss manufacturer Cortébert. The main driving forces behind the production of the first professional diving watches were Hans Wilsdorf of Rolex and Giuseppe Panerai.

The Florence-based workshop produced wrist-worn diving instruments and, between 1935 and 1970, delivered around 1,600 watches (c. 35 2533s, 1000 3646s, 24 6152s, 36 6154s, 500 6152/1s, and 60 GPF 2/56s), most of them to the Italian Marina Militare. All watches, except for the GPF 2/56, were made by Rolex, and G. Panerai e Figlio produced only the dials for these watches. Panerai dials were rendered luminous with Radiomir, a highly radioactive radium-based self-luminous compound, and later in around 1965, with Luminor, a harmless compound activated by tritium.