Antonio Pignatelli was born on 13 March 1615 in Spinazzola[1] (now in Apulia) to one of the most aristocratic families of the Kingdom of Naples, which had included several Viceroys and ministers of the crown.

Pope Alexander VIII died in 1691 and the College of Cardinals assembled to hold a conclave to select his successor.

Factions loyal to the Kingdom of France, Spain and the broader Holy Roman Empire failed to agree on a consensus candidate.

[2] Having received 53 out of 61 votes, Pignatelli took his new name in honour of Pope Innocent XI and was crowned on 15 July 1691 by the protodeacon, Cardinal Urbano Sacchetti.

Immediately after his election on 12 July 1691, Innocent XII declared his opposition to the nepotism which had afflicted the reigns of previous popes.

[1] At the same time he sought to check the simony in the practices of the Apostolic Chamber and to that end introduced a simpler and more economical manner of life into his court.

Innocent XII was already considerably ill on 25 December 1699 with gout (a rheumatic disease) and was therefore unable to attend the solemn opening of the Holy Door at Saint Peter's Basilica to mark the beginning of the Jubilee for 1700, hence, Cardinal Emmanuel-Théodose de La Tour d'Auvergne represented the pontiff in the solemn celebration.

On Easter Sunday in 1700, the seriously ill pontiff gave a blessing from his balcony to the large crowds outside of the Quirinal Palace.

Innocent appears as one of the narrators in Robert Browning's long poem The Ring and the Book (1869), based on the true story of the pope's intervention in a historical murder trial in Rome during his papacy.