Luxardo  was founded in 1821 by Girolamo Luxardo in the city of Zara, which is now known as Zadar. Luxardo had moved to Zara with his family in 1817, as the consular representative of the Kingdom of Sardinia. His wife (Maria Canevari) produced liqueurs at home, specializing in "rosolio maraschino", a liquor from Dalmatia, and Luxardo founded the distillery to produce Liquore Maraschino. Girolamo Luxardo died in 1865 at age 81, and his son Nicolò took over the business.In 1913 a new distillery was built by Michaelangelo Luxardo, who was of the third generation of Luxardos. The distillery was one of the largest in the Austro-Hungarian Empire. The building still stands today.

The distillery was almost completely destroyed by Allied bombings during the Second World War. In 1944, at the end of German occupation, the city was seized by Josip Broz Tito's troops, then ceded to Yugoslavia at the end of the war. Almost all the Italian citizens, and among them most of the Luxardo family were forced to flee (exodus from Istria and Dalmatia), and some of them were murdered, like Nicolò Luxardo, his wife Bianca Ronzoni and his younger brother Pietro. The business was temporarily refounded in Venice by Giorgio Luxardo, before Giorgio moved to Torreglia, near Padova, in the Veneto region of Italy, where he built a new distillery and continued the family's and firm's activities. The sixth generation of the family is still active in the operations of the company, including: Piero Luxardo, Franco Luxardo, Guido Luxardo, Matteo Luxardo, Filippo Luxardo and Giorgio Luxardo.

Today Luxardo are the producers of a wide array of drinks, including Sambuca, Amaretto and Liqueurs.