[1] When the opera was staged in Paris (Théâtre des Italiens) in 1840, Victor Hugo obtained an injunction against further productions within the domain of French copyright law.

Lucrezia was first presented in New Orleans on 27 April 1843 and then at New York's American Theatre on 11 May 1843[1] and later at the Palmo's Opera House in 1847: with Giulia Grisi in 1854; and with Thérèse Tietjens and Brignoli in 1876.

A famous performance of Lucrezia Borgia presented by the American Opera Society Ensemble in 1965 at Carnegie Hall with soprano Montserrat Caballé, who was making her American debut, was soon followed by a recording featuring Caballé, Shirley Verrett, Alfredo Kraus, and Ezio Flagello, conducted by Jonel Perlea, who also led the Carnegie Hall performance.

Lucrezia Borgia is often produced as a vehicle for a star soprano, including Leyla Gencer, Mariella Devia, Beverly Sills, Dame Joan Sutherland, Renée Fleming, Edita Gruberová and Sondra Radvanovsky.

The Palazzo Grimani in Venice Gennaro and his friends, including Orsini, celebrate on the brightly lit terrace, in front of which lies the Giudecca Canal ("Bella Venezia!").

On hearing Lucrezia's name, Orsini tells of how Gennaro and he, alone in a forest, were warned by a mysterious old man to beware her and the entire Borgia family, and that the two of them would die together ("Nella fatal di Rimini").

The others return ("Gente appressa... io ti lascio") and seem to recognise her, listing in turn the members of their families she has killed, to Gennaro's horror and disbelief ("Maffio Orsini, signora, son'io").

Ferrara The Duke, believing Gennaro to be Lucrezia's lover, plots his murder with his servant Rustighello ("Vieni: la mia vendetta è meditata e pronta").

In a scene full of drama and tension, she denies any impropriety, but he demands the prisoner's death and forces her to choose the manner of Gennaro's execution.

The closing cabaletta "Era desso il figlio mio" was added by Donizetti upon insistence by renowned soprano Henriette Méric-Lalande, who created the role of Lucrezia Borgia.