Murillo is one of the leading exponents of the Seville Baroque school of painting. He was familiar with the works of the Flemish and Venetian painters of the day, and also those of Ribera and Zurbarán. In 1645 he achieved his first success with his eleven paintings for the Franciscan friary of Seville, works which betray the influence of Ribera, Velázquez and Zurbarán. This period, in which the influence of Zurbarán's chiaroscuro style can still be made out, includes such works as The Holy Family with a Little Bird, The Virgin of the Rosary, and depictions of children such as Children Eating Fruit and Child Beggar. The backgrounds of these paintings are dark, almost devoid of detail, and the figures stand out as lively and engaging.
Towards 1650 the painter entered his richest vein, above all reproducing images of the Immaculate Conception. At a time of such religious fervour, this went down very well and won Murillo great acclaim. His fine religious works, including also martyred saints, lack the earthiness of Ribera or the mysticism of Zurbarán. They are portraits of figures of his day, dressed in current fashions and located in peaceful settings: Saint Justa and Saint Ruffina, Saint Leander and Saint Bonaventure.
Between 1660 and 1670, he produced a series of paintings for the Church of Saint Mary the White in Seville, in which he achieved beautifully luminous effects, highlighting the realism of the commonplace, and recalling the biblical works of Rembrandt. Particular mention within this series, based on the founding of Saint Mary Major in Rome, should be made of The Dream of Patrician John, Patrician John Reveals his Dream to Pope Liberius. Between 1670 and 1674 he painted a major series of works for the Hospital of Charity of Seville: Saint John of God, Saint Elizabeth of Hungary, The Miracle of the Loaves and the Fishes.
Murillo was also an outstanding portraitist. His subjects are not adorned in the rich vestments of courtesans, but are members of the aristocracy or clergy of Seville, and are depicted in poses of elegant dignity. Murillo's genre painting is also of significance: these are works of tremendous naturalism, featuring rogues, beggars and urchins, the characters of Spanish 17th century picaresque novels: Boys Eating Melon, The Little Fruit Sellers, Beggar, among others.