A pupil of Francesco Morelli, he worked mainly in Rome, initially with a late-Mannerist style. He was also nicknamed Il Sordo del Barozzo. He published two books, The nine churches of Rome (1639) and The Lives of Painters, Sculptors, Architects and Engravers (active from 1572-1642). The last title is still seen as an important historical source for painters living in Rome during the life of Baglione.

Among those he chronicled, and for whom he was notorious in his animosity was Caravaggio, whose style had influenced him. The latter was forced to leave the city after Baglione's accusations of sodomy. Baglione's Sacred love versus profane love, a response to Caravaggio's Love Victorious, shows an angel (Sacred Love) interrupting a 'meeting' between Cupid (Profane Love) and the Devil (portrayed with the face of Caravaggio).

He was employed in many works in Rome during the pontificates of Clement VIII and Paul V. His main works are frescoes which can be seen in the Santa Maria Maggiore in Rome, in the Cappella Borghese. For the church of Santa Maria dell'Orto he painted in the chapel of Our Lady with the Zuccheri scenes from the life of the Blessed Virgin.

Among other works which he executed for this church is a painting of Saint Sebastian. An excellent example of Baglione's work is The Last Supper at San Nicola in Carcere. He also painted Saint Stephen in the Cathedral at Perugia. Pope Paul V knighted Baglione a Knight of the Order of Christ for his painting of Saint Peter Raising Tabitha from the Dead (1607) in St. Peter's Basilica. He also painted a St. Stephen for the cathedral of Perugia, and a St. Catharine for the cathedral of Loreto. He died in Rome.