Veronica Franco [Catherine McCormack] is an adventurous, curious, and slightly tomboyish young woman in Venice. Her love, Marco Venier [Rufus Sewell], who will be a Senator like his father, cannot marry her because her family is too poor; he marries a foreign noblewoman instead.
Paola Franco [Jacqueline Bisset], Veronica's mother, plans for her family's financial security, as she still requires dowries for her younger daughters and money for her son's commission. Rather than go to a convent, Paola suggests Veronica become a courtesan, a highly paid, cultured prostitute like her mother and grandmother before her.
At first Veronica is repelled by the idea, but once she discovers that courtesans are allowed access to libraries and education, she tentatively embraces the idea. Training under her mother's tutelage, Veronica is shown how to seduce men subtly, even from afar.
Impressing the powerful men of Venice with her beauty, wit, and compassion, Veronica quickly gains a reputation as a top courtesan. Marco finds it difficult to adjust to his new wife, who is nothing like Veronica, and becomes jealous as Veronica takes his friends and relatives as lovers.
Marco's cousin, Maffio Venier [Oliver Platt], a poor bard who was once publicly upstaged and later rejected by Veronica, attacks her due to envy. They have a duel of words as well as swords, after which Marco rushes to Veronica's aid. Although Marco and Veronica rekindle their romance, she refuses to stop seeing clients and accept his support. Nevertheless, Veronica spends a great deal of time with Marco, neglecting her business and ignoring her mother's warnings that such a relationship is dangerous for her.
The Fourth Ottoman–Venetian War (1570–73) breaks out, and the city appeals to France for aid. In order to secure a military alliance, Veronica is encouraged to seduce the King of France, which she does.
Accusing Veronica of enjoying being a courtesan, Marco implies she ought to have rejected the King despite the risk to Venice. Veronica points out that she sacrificed their love for the good of the city, while he only did it to protect his family's political standing, so Marco leaves for war angry.
Being better connected and educated than the noblewomen left behind, Veronica is called to inform them of the war's progress. Soon ejected from the gathering, she and her noblewoman friend have a private conference, where she is asked to one day train her daughter to be a courtesan. Veronica points out she is not much freer in the end, having to plan to support herself in her old age.
While the Venetians are fighting at sea, a plague hits the city. Religious zealots take the war and plague as punishment for the city's moral degradation, and Veronica's home is quarantined and almost ransacked by a mob. Marco returns before Veronica is charged and just before Paola dies of the plague.
Veronica is summoned to appear before the Inquisition on charges of witchcraft. Maffio, who is now a monsignor, leads the forces against Veronica, and Marco accuses him of having a personal vendetta against her. Marco declares that if she is guilty, then he—along with many others present—is her accomplice. Even when it appears that she will be executed, Veronica refuses to name her clients. Marco publicly shames the Venetian ministers and senators into admitting their own adulteries and sins by standing up in the assembly. Bewildered by the extent of sin in the city, and unwilling to attack so many powerful men, the Inquisitor drops the charges of witchcraft.
Marco and Veronica were lovers the rest of their days.
