Bianca was a daughter of Piero di Cosimo de' Medici and Lucrezia Tornabuoni. In 1459, she married Guglielmo de' Pazzi, who was a childhood friend of her brother, Lorenzo de' Medici. This alliance was intended to help resolve the animosity between the families, but it was not successful in that regard as Machiavelli noted in his Florentine Histories. Their first child, Antonio, was born in 1460. The marriage agreement included a significant reduction in taxes imposed on the Pazzi family. In the aftermath of the Pazzi conspiracy of 1478, Bianca's marriage significantly softened Lorenzo's wrath towards Guglielmo, who was only put under house arrest for a time, while his male relatives were exiled or executed; his daughters were exempted from the marriage ban imposed on other Pazzi daughters.
In 1460, Bianca was asked to play the organ for Pope Pius II and his entourage during a visit to Florence, as the pope was coming back from the Council of Mantua. Teodoro Montefeltro, the Apostolic protonotary travelling with the pope, praised the performance in a letter to Barbara of Brandenburg, Marquise of Mantua. During the same papal visit, she performed a second concert for the future pope Rodrigo Borgia at his request. Bianca often performed for local and visiting dignitaries, contributing to her families' reputation and influence.
In 1475, Bianca asked her mother to purchase farmland from other relatives for her, as Lucrezia had more influence within the family. Though Bianca owned the property, it was managed by staff employed by her mother.
