Belonging by birth to the House of Brignole-Sale, one of the most prestigious aristocratic families in Genoa and one which had produced several doges, she was born in the city's Palazzo Rosso to Antonio Brignole Sale, 11th Marquess of Groppoli and his wife Artemisia Negrone.
Antonio's mother Anna Pieri had been a lady-in-waiting to Napoleon's second wife Marie Louise, whilst his sister Maria Pellegrina had married duke Emmerich von Dalberg, second only to Talleyrand in the French diplomatic corps.
Maria herself called it "comfortable so long as one did not have children" and her husband little by little furnished it with the Brignole family art collection, starting with portraits by Anthony van Dyck and Hyacinthe Rigaud.
Their third child Filippo (1850–1917) became an eccentric stamp-collector and found relations with his mother strained by her nostalgia for his two dead siblings and her sympathy for new socialist ideas.
Raffaele had in the meantime become senator of the Kingdom of Italy in 1858 and – now effectively without an heir thanks to Filippo's decisions – he decided to devote himself to public works and philanthropy, giving 20,000,000 lira to improve the Port of Genoa, money which also funded the construction of several other pieces of infrastructure, most notably the Galliera, Lucedio and Giano jetties.
The Villa Brignole Sale Duchessa di Galliera in Voltri was left to a charitable "opera pia" – since 1931 it has been used and part-owned by the city council of Genoa.