[2][3] Thanks to the efforts of her mother Renée, who invited talented teachers to the Ferrarese court, Lucrezia and her sisters, Anna and Eleonora, received an excellent education.

Duke Guidobaldo II della Rovere didn't interfere with his daughter-in-law's hobbies of poetry, music and theatrical performances.

Her relationship with her younger husband was always difficult: without hesitation, the Duke pointed out that the failure of having children was Lucrezia's fault due to her old age, despite the fact that he himself infected her with syphilis.

[11][12][13] During these years, Lucrezia found a great source of consolation in her friendship with Torquato Tasso, who was on duty at the Duchess's court in Pesaro and Urbania.

[10] After her lover Count Ercole Contrari was killed in 1575 by her brother Alfonso II upon discovery of their relationship, Lucrezia had increasingly tense and difficult relations with other family members of the House of Este.

This was a crucial political phase that saw the publication in 1567 of the Papal Bull Prohibitio alienandi et infeudandi civitates et loca Sanctae Romanae Ecclesiae by Pope Pius V, which prohibited illegitimate children (or the descendants) from being invested in Church fiefdoms.

Lucrezia was an important and decisive ally for the Papacy in this matter as she was completely hostile to her brother's designated heir, Cesare d'Este, who feared being excommunicated by Pope Clement VIII.

[2] However, Cesare, trusting in Lucrezia's proximity and her contacts with Rome and underestimating the hatred she had for him and the Este dynasty, sent her to meet Cardinal Pietro Aldobrandini, the Papal legate designated to take possession of Ferrara.

An agreement was reached whereby the Holy See took effective control not only over Ferrara, but also other territories which weren't Papal fiefs with certainty and that could have remained with the House of Este, such as Comacchio, Lugo, Bagnacavallo and Conselice.

Lucrezia was able to retain for her family the Duchies of Modena and Reggio, whose investiture was secured by Rudolph II, Holy Roman Emperor.