The church was designed by Giacomo della Porta and built by Domenico Fontana between 1518 and 1589, and completed through the personal intervention of Catherine de' Medici, who donated to it some property in the area.

By the end of the tenth century, the Abbey of Farfa owned in Rome churches, houses, windmills and vineyards.

Giacomo della Porta made the façade as a piece of decorative work entirely independent of the body of the structure, a method much copied later.

[10] The French character is evident from the façade itself, which has several statues recalling national history: these include Charlemagne, St. Louis, St. Clothilde and St. Jeanne of Valois.

Other works in the church include pieces by Cavalier D'Arpino, Francesco Bassano il Giovane, Muziano, Giovanni Baglione, Siciolante da Sermoneta, Jacopino del Conte, Tibaldi and Antoine Derizet.

The church was chosen as the burial place for a number of higher prelates and members of the French community of Rome:[11] these include the classic liberal economist Frédéric Bastiat, Cardinal François-Joachim de Pierre de Bernis, ambassador in Rome for Louis XV and Louis XVI,[12] and Henri Cleutin, the French Lieutenant in 16th-century Scotland.

[14] The inscriptions found in San Luigi dei Francesi, a valuable source illustrating the history of the church, have been collected and published by Vincenzo Forcella.