While chasing his falcon through the fields, a rich young bachelor named Calisto enters a garden where he meets Melibea, the daughter of the house, and is immediately taken with her. Unable to see her again privately, he broods until his servant Sempronio suggests using the old procuress Celestina. She is the owner of a brothel and in charge of her two young employees, Elicia and Areúsa.
When Calisto agrees, Sempronio plots with Celestina to make as much money out of his master as they can. She rewards him with Elicia. Another servant of Calisto's, Pármeno, mistrusts Celestina because he used to work for her when he was a child. Pármeno warns his master not to use her. However Celestina convinces Pármeno to join her and Sempronio in taking advantage of Calisto. His reward is Areúsa.
As a seller of feminine knick-knacks and quack medicines, Celestina is permitted entrance into the home of Alisa and Melibea by pretending to sell thread. Upon being left alone with Melibea, Celestina tells her of a man in pain who could be cured by the touch of her girdle. When she mentions Calisto’s name, Melibea becomes angry and tells her to go. But the crafty Celestina manages to get the girdle off her and to fix another meeting.
On her second visit, Celestina persuades the now willing Melibea to a rendezvous with Calisto. Upon hearing of the meeting set by Celestina, Calisto rewards the procuress with a valuable gold chain. The two lovers spend the night together in Melibea's garden, while Sempronio and Pármeno keep watch.
When the weary Calisto returns home at dawn to sleep, his two servants go round to Celestina’s house to get their share of the gold. She tries to cheat them and in rage they kill her in front of Elicia. After jumping out of the window in an attempt to escape the Night Guard, Sempronio and Pármeno are caught and are beheaded later that day in the town square. Elicia, who knows what happened to Celestina, Sempronio, and Pármeno, tells Areúsa of the deaths. Areúsa and Elicia come up with a plan to punish Calisto and Melibea for being the cause of Celestina, Sempronia, and Pármeno's downfall.
After a month of Calisto sneaking around and seeing Melibea at night in her garden, Areúsa and Elicia enact their plan of revenge. Calisto returns to the garden for another night with Melibea; while hastily leaving because of a ruckus he heard in the street, he falls from the ladder used to scale the high garden wall and is killed. After confessing to her father the recent events of her love affair and Calisto's death, Melibea jumps from the tower of the house and dies too.