Guercino received his earliest training locally, but the formative influence on his style came from Bologna, especially from the naturalistic paintings of Lodovico Carracci. Such early works as “Madonna in Glory with Saints and a Donor” (1616; Royal Museum of Fine Arts, Brussels) have large forms, strong colour, and broad, vigorous brushwork. His method of using light and shadow was unrelated to the discoveries of Caravaggio and was derived from Bologna and Venice, which Guercino visited in 1618.

In 1621 Guercino went to Rome, where he played an important role in the evolution of Roman High Baroque art. Among many other commissions, he decorated the Casino Ludovisi. The main fresco, “Aurora,” on the ceiling of the Grand Hall, is a spirited romantic work, painted to appear as though there were no ceiling, so that the viewer could see Aurora's chariot moving directly over the building. Yet it already reveals something of the crucial experience of his stay in Rome, his contact with Pope Gregory XV's private secretary, Monsignor Agucchi, a propagandist for the classicism of Annibale Carracci's balanced and restrained Roman style. Guercino seems to have tried to make his own style conform with Carraccesque principles, an effort reflected in his “Sta. Petronilla” (1621; Capitoline Museum, Rome). On the death of Gregory XV in 1623, Guercino opened a studio in Cento. Then, upon the death of Guido Reni (1642), whose position in Bologna as heir to Annibale Carracci had been unassailable, he moved to that city, where he was the leading painter until his death.

Some of Guercino's late works, such as “Abraham Driving Out Hagar and Ishmael” (1657–58; Brera Picture Gallery, Milan), are impressive achievements, but other paintings seem weak or sentimental.