Following in the footsteps of his uncle Alessandro Ludovisi, he was trained at the Jesuit Collegio Germanico of Rome, and went on to the University of Bologna, where he received his doctorate in canon law on 25 February 1615.

When Alessandro Ludovisi was acclaimed pope, taking the name Gregory XV, Ludovico was made cardinal the day after his coronation, though he was only 25.

His uncle had great faith in his judgement and energy and was in need of a strong and able assistant to help govern the Papal States (the Pope was, after all, in his late 60s).

As the Catholic Encyclopedia avers:[1] Ludovico, it is true, advanced the interests of his family in every possible way, but he also used his brilliant talents and his great influence for the welfare of the Church, and was sincerely devoted to the pope.He was sent as legate in Fermo in 1621 and in Avignon, 1621–1623.

He rapidly assembled from private owners and the Carmelite brothers of Santa Maria in Traspontina a holding of vineyards and small plots to create the Villa Ludovisi, a vast complex of gardens and buildings on the Monte Pincio near Porta Pinciana, in the so-called "Gardens of Sallust" on the site where Julius Caesar and his heir, Augustus, had had their villas.