Most of Zurbarán's paintings of female saints were commissioned as series and executed largely by assistants. In 1647 he received an order for twenty-four canvases of Virgin Saints for Lima, and in 1649 one for fifteen destined for Buenos Aires. His painting of Saint Margaret, probably of the early or mid-1630s, is unusual in being an autograph work and not apparently one of a series. The saint was a virgin martyr of 4th-century Antioch. She was believed to have overcome a dragon and is shown with a shepherd's crook in reference to the legend that she was responsible for grazing the sheep of her nurse.

In Zurburán's painting she is represented in picturesque costume with a saddle bag ('alforjas') over her arm, a book in her hand, and oblivious to the dragon at her side. Her head and dress show to advantage the careful and smooth technique of the painter, attentive to the definition of detail.