Giuseppe was the son of Anton Giulio Brignole-Sale, 5th Marquess of Groppoli (1673–1710) and Isabella Brignole, one of the most powerful and wealthy families in the Republic of Genoa.
While at Versailles, his wife started an affair with the young Honoré III, Prince of Monaco and when she suggested that their daughter marry her ex lover, Brignole refused fearing for his reputation.
Honoré III pressured for seventeen months but then opened negotiations to marry the daughter of the Duke of La Vallière.
However, the French King Louis XV spoiled the relations between Honoré III and the Duke of La Vallière.
Negotiations then changed and their daughter Maria Caterina married Honrore III by Proxy on 15 June 1757.