Built in Baroque style between 1626 and 1650, the church functioned originally as the chapel of the adjacent Roman College, which moved in 1584 to a new larger building and was renamed the Pontifical Gregorian University.

[1] It is one of the great 17th century preaching churches built by Counter-Reformation orders in the Centro Storico (the others being The Gesù, also of the Jesuits, San Carlo ai Catinari of the Barnabites, Sant'Andrea della Valle of the Theatines, and the Chiesa Nuova of the Oratorians).

The Collegio Romano opened very humbly in 1551, with an inscription over the door summing up its simple purpose: "School of Grammar, Humanity, and Christian Doctrine.

[5] The nuns had already started to build what had been intended to become the Church of Santa Maria della Nunziata,[6] erected on the spot where the Temple of Isis had stood.

A three-aisled church dedicated to the Most Holy Annunciation (Italian: Santissima Annunziata) was built by the Collegio Romano between 1562 and 1567 on the foundations of the pre-existing construction.

Since the earlier church had already been built to the height of the ground floor in 1555, there was no way for the Jesuits to expand the structure to hold the increasing number of students attending the Collegio Romano.

Following the canonization of Ignatius of Loyola in 1622, he suggested to his nephew, Cardinal Ludovico Ludovisi, that a new church dedicated to the founder of the Jesuits should be erected at the college itself.

The foundation stone was laid only on 2 August 1626, four years later, a delay which was caused by the fact that a section of the buildings belonging to the Roman College had to be dismantled.

The imposing order of Corinthian pilasters that rings the entire interior, the theatrical focus on the high altar at the rear of the broad eastern apse, the church's colored marbles, animated stucco figural relief, richly ornamented altars, extensive gilding, and bold trompe-l'œil paintings in the "dome" at its crossing and in the nave ceiling all produce a festive, sumptuous effect.

By the skilful use of linear perspective, light, and shade, he made the great barrel-vault of the nave of the church into an idealized aula from which is seen the reception of St. Ignatius into the opened heavens.

A second marker in the nave floor further east provides the ideal vantage point for the trompe-l'œil painting on canvas that covers the crossing and depicts a tall, ribbed and coffered dome.

The original painting, completed in 1685, was destroyed by fire; in 1823 it was faithfully reproduced by Francesco Manno on the basis of drawings and studies left by the Pozzo.

The chapel in the left transept has a marble altarpiece of the Annunciation by Filippo Della Valle, with allegorical figures and angels (1649) by Pietro Bracci, and a frescoed ceiling with The Assumption by Pozzo.