In 1615 Ludovico received a doctorate in Canon law at the University of Bologna, later continuing his education in the Jesuit Collegio Romano and began working at the Curia. However, his true career began in 1621, when his sickly uncle Alessandro Ludovisi became pope, taking on the name of Gregory XV. Ludovico was at his side immediately after his nomination and almost daily he had to count on the death of his protector, who entrusted him with the highest church and administrative posts in the State of the Church. During the short pontificate of his uncle – which lasted only 29 months- he acquired astronomical sums. He used them for the construction of a suburban residence and the founding of a church, which was to be a testimony of the greatness of the Ludovisi family and was to emphasize the inseparable connection with the Order of the Jesuits. The Church of Sant’Ignazio, was to become a breath-taking church, commemorating the founder of the order, St. Ignatius of Loyola, but also the pope and his nepot, who canonized the former. This was possible thanks to the enormous sums (200 thousand scudos) invested at the beginning of the construction as well as the appropriate deposits guaranteed by the testament.

The cardinal appointed his co-workers from the ranks of the Jesuits. In a politically complicated system of clients and enemies of the pope it was difficult for Ludovico to obtain devoted and loyal members of the clergy in the Curia itself. The frail health of Gregory XV carried with it the danger of his imminent death, which would result in the end of the nepot’s career and disfavor of the following bishop of Rome, as that was the reality of the then Vatican politics. The collaborators of one pope could only count upon him, the next could not only discharge them, but even destroy, depending on how strong the dislike was for his predecessor. The well-educated and loyal Jesuits at the side of Pope Gregory XV, constituted the strength of him and his nepot, which they were to pay a high price for in later years. Temporarily, The Order of the Jesuits gained the pope’s protection despite attacks of some members of the Curia, as well as the Dominicans and the Franciscans, who looked disfavorably upon the successes of Jesuit missionaries, accusing them of far-reaching deviations from Christian orthodoxy. In the name of his sickly uncle, Ludovico also conducted dynamic family policy, arranging marriages, for example, with representatives of the Aldobrandini family.

However, by posterity cardinal Ludovisi will be remembered as a great collector and patron of art, who in a relatively short time amassed a collection of antique objects comparable to that gathered by his rival and competitor - Scipione Borghese. Apart from a few exceptions he was not interested in contemporary art. His collections can be seen in the Roman Museo Nazionale Romano – Palazzo Altemps, while the most valuable from the objects exhibited there still today are known as Ludovisi (Ludovisi Hera, Ludovisi Throne). The cardinal’s collection was imposing indeed – 216 sculptures and bas-reliefs, 94 busts and other antique items, which were found in his suburban residence. Out of all the buildings which were a part of it, only Casino Ludovisi remains until the present day with outstanding paintings of the artist favored by the cardinal – Guercino.

The death of Pope Gregory XV, came about in 1623. At the following conclave, Ludovisi sympathized with the Spanish camp, of which the interests were in opposition to the pro-French camp of Maffeo Barberini – the final victor of this battle. After his election as pope (who assumed the name of Urban VIII), Ludovico fell into conflict with him. Initially it was not too severe, but later it became stronger, which caused Ludovisi to leave his magnificent residence (Villa Ludovisi), leaving the works at the Church of Sant’Ignazio unfinished, and going to Bologna where the cardinal quickly died at the age of 37, due to arthritis. His body was brought from Bologna to Rome in 1632, and placed in a makeshift grave, planned in the Church of Sant’Ignazio. He had to wait for a tomb nearly one hundered years. However, it was worth it – he was commemorated along with his uncle in a huge, monumental tombstone statue in 1717.