Just over one month after his ordination to the priesthood, Pier Luigi was elected titular archbishop of Larissa in Thessalia on 27 March 1713 and then made an Assistant at the Pontifical Throne on 16 April 1713.

Archbishop Carafa was created cardinal-priest in the consistory of 20 September 1728 and received the red galero and the title of San Lorenzo in Panisperna, where he was installed on 15 November 1728.

His remains were transferred the following day to the church of Sant'Andrea delle Fratte in Rome where the capella paplis took place on 18 December 1755, and he was buried in the chapel of Saint Francis de Sales.

[1] On the funerary plaque of Cardinal Pier Luigi Carafa in the chapel of Saint Francis de Sales, the following in Latin is inscribed:

Pier Luigi Cardinal Carafa is entombed in the chapel of Saint Francis de Sales in the Church of Sant'Andrea delle Fratte in Rome.