The story is set in the seventeenth century, in the Duchy of Milan, then a Spanish possession in northern Italy; however, the plot is merely a pretext for the author to weave a timeless and universal tale that touches on every human feeling, passion, and behavior.

In compelling fashion, love, hate, prejudice, vengeance, forgiveness, fear, courage, crime, punishment, redemption, treachery, loyalty, religion, superstition, love of country, devotion to duty, generosity, greed, art, science, politics, economics, and emigration come together in this book, making it, unquestionably, one of the giants of foreign literature.

The book opens as two of Don Rodrigo's toughs order the local parish priest, Father Abbondio, not to marry Lucia to Renzo--she a beautiful, honest and deeply religious country girl, he a sensible, upright and God-fearing craftsman. Don Rodrigo is an arrogant aristocrat able to impose his will on those around him thanks to an overall social structure that favors the powerful and preys on the downtrodden. He has forbidden the marriage because he has bet his cousin that he will seduce Lucia, and has set a deadline for his deed.

The fearful priest obeys Don Rodrigo's order, but a saintly monk, Brother Christopher, tries to dissuade him from lusting after the girl. Irritated by the friar's plea, Don Rodrigo decides to kidnap Lucia, to be certain of possessing her before the expiration of the bet deadline.

He fails because Lucia is not at home at the time of the attempted abduction. Trying to take advantage of a loophole in the law which allows two people to declare themselves man and wife (provided a priest is present), she and Renzo have gone to Father Abbondio's residence, to force him to witness their exchange of vows. However, Father Abbondio, afraid of Don Rodrigo's retribution, foils the two young people's attempt. His screams cause his sexton to ring out the general alarm from the church's bell tower. The fiancés, the would-be kidnappers, and the entire village are thrown in total disarray.

Brother Christopher helps Lucia find safe haven in a convent, and makes arrangements for Renzo to find work in Milan, away from Don Rodrigo's fury. Immediately after arriving in Milan, Renzo is, however, caught up in a bread riot sparked by a government-decreed price increase. He is framed and arrested as one of the riot ringleaders, but is able to escape to a neighboring country, where he is forced to disguise his identity.

Since Don Rodrigo's is not powerful enough to infiltrate Lucia's place of asylum, he seeks the help of another man, "whose long arm often reached farther than his enemies' eyes." Lucia is treacherously abducted and taken to this ferocious overlord's castle, from where she is to be turned over to Don Rodrigo.

However, the overlord has secretly been harboring serious concerns over his past crimes. Lucia's plight and pleadings help precipitate his crisis of conscience. He goes to see Cardinal Federigo, who is on a pastoral visit in a nearby village, and, with the Cardinal's encouragement, decides to change his way of life.

Lucia is freed unharmed, but is still unable to return home because of the ever present threat from Don Rodrigo. So, she goes to live in Milan, under the protection of a powerful, well meaning, but rather eccentric couple. There, she has to wage a constant struggle with herself, because on the night of her abduction she had made a vow that she would remain a virgin if she could safely come out of that predicament. Though still deeply in love with Renzo, she is determined to keep her vow because of her strong religious faith.

War, famine and pestilence further complicate the lives of the two young people but, at long last, Renzo is able