Probably before 1630, Preti joined his brother Gregorio (also a painter), in Rome, where he became familiar with the techniques of Caravaggio and his school as well as with the work of Guercino, Rubens, Guido Reni, and Giovanni Lanfranco.

In Rome, he painted fresco cycles in the churches of Sant'Andrea della Valle and San Carlo ai Catinari.

Preti's major works include a series of large fresco ex-votos depicting the Virgin or saints delivering people from the plague, which were painted on seven city gates and are now lost - two sketches for them are in the Capodimonte Museum in Naples,[3] including a bozzetto of the Virgin with the baby Jesus looming over the dying and their burial parties which envisions a Last Judgement presided over by a woman.

[4] Preti also won a commission to supervise the construction, carving, and gilding for the nave and transept of San Pietro a Maiella, along with producing a Judith and Holofernes and Saint John the Baptist, both still in Naples.

His paintings, representative of the exuberant late Baroque style, are held by many great museums, including important collections in Naples, Valletta, Palermo, and in his hometown of Taverna, Calabria.