In 1849 he moved to California, upon the recomendation of his former neighbor, James Lick, who had brought 600 pounds of chocolate with him to San Francisco in 1848. Caught up in the gold rush, Ghirardelli spent a few months in the gold fields near Sonora and Jamestown, before deciding to become a merchant in Stockton. In 1852, he moved to San Francisco and established the Ghirardelli Chocolate Company at Ghirardelli Square.
About 1865 Ghiradelli discovered that by hanging a bag of chocolate in a warm room, the cocoa butter will drip off, leaving behind a residue that can then be converted into ground chocolate. This technique, known as the Broma process is now the most common method for the production of chocolate.
In 1894, while on a trip to his birthplace in Italy, Domingo Ghirardelli died.