The youngest of ten children, he was born in Sestri Levante, then part of the independent Republic of Genoa, to Bernardo and Pellegrina Raggi Lambruschini, and baptized Emmanuele Nicolo.

[1] Lambruschini attended a Jesuit school in Santa Margherita Ligure, and then the Oratorio di San Bartolomeo in Bordighera, run by the Order of the Barnabites.

It was rumored that his promotion was to be attributed to the desire of Secretary of State Consalvi to remove from Rome a clergyman who, having acquired too much influence on the pope, was now an obstacle to his own plans for government.

[1] In 1826, he was named as Apostolic Nuncio to the Kingdom of France by Pope Pius VII, but was forced to flee his diplomatic post following the 1830 revolution that toppled the Bourbon monarchy and brought House of Orleans pretender Louis-Phillippe to the French throne.

[4] For the next four years, Cardinal Lambruschini held various curial posts until in January 1836 he was appointed Secretary of State to Pope Gregory XVI.

His appointment was seen as a compromise between those who hoped for reform and the zealanti who wished to see dissent more forcefully suppressed; although it was said that the Cardinal was "liberal chiefly in his employment of spies and prisons".

He was eventually defeated by the liberal candidate, Giovanni Maria Mastai Ferretti, the Archbishop (personal title) of Imola, who became Pope Pius IX.

Some descendants of these brothers stayed in Italy, others moved to France, the United States and even South America (Peru, Chile, Argentina, and Uruguay).