The story of Lucretia is part of the legendary history of early Rome. Lucas Cranach's sensual rendering of her in this painting underscores a Northern Renaissance visual tradition of the dual role of women as both temptresses and morally upright beings. Cranach was an enormously successful artist who worked for the Saxon princes and courtiers in Wittenberg, Germany. Particularly popular were his paintings that featured nude women in subjects from Roman mythology and classical history.

The Suicide of Lucretia depicts the virtuous wife of a Roman nobleman. The morning after she was raped by the king's son, she told her father and husband what had happened, and then she fatally stabbed herself.

Her suicide enraged the people of Rome, who expelled the ruling family, laying the foundation for the establishment of a republic. Cranach and his workshop painted dozens of versions of Lucretia's story. This painting is believed to be one of the primary versions, because—unlike many of the others—inscribed on the ledge behind the figure of Lucretia is Cranach's monogram, and, most unusual, the date of the painting's execution.