By 1503, the Papal guards protected Pope Alexander VI, and were led by the Pope's son and Captain General, Cesare Borgia. Following the fall of the Borgia, they were once again commanded by their former captain Fabio Orsini. They were also the precursors to the Swiss Guard.
The Papal guards were the most versatile and difficult guards in Rome, as they possessed the best of abilities held by all other archetypes. They were skilled in both attack and defense, easily deflecting and countering many attacks, while also delivering harsh strikes of their own.
Papal guards could dual-wield a wheel-lock firearm and a sword, making them deadly opponents at both short and long-range. Other than swords, they could also be equipped with a variety of short, long, or heavy weapons, though guards utilizing these were rarer to witness.
Much like Agiles, Papal guards were extremely fast, and were able to dodge most attacks. Accompanying this, they were also difficult to escape from, and could even catch up to Assassins in a chase.
Papal guards often traveled in groups, and would employ teamwork strategies in battle. While one could continuously fire at their target from a distance, the others would attack from close range. As well as this, they could throw sand and grab enemies from behind, skills common to Seekers.
- Historically, the Papal Guard was comprised mostly of Swiss soldiers from its conception in 1471, when Pope Sixtus IV made a pact with the Swiss to supply him with mercenaries. Although these mercenaries primarily protected the Pope, they also occupied leadership roles on the front lines of the Italian Wars.
- In the memory "Liquid Gold", the guard captain can be heard speaking German, proving their Swiss nationality.
- Early Papal guard designs were seen in the Assassin's Creed: Brotherhood cinematic trailer, and in Assassin's Creed: Ascendance. While the designs for the guards themselves were changed before the game's release, Fabio Orsini wore the same armor as seen in the original concept, albeit without a helmet and bearing a different emblem.
- Additionally, all the Papal guards seen were shown to have halberds. However, in-game, the only time they could be seen carrying halberds was during the arrest of Cesare Borgia.
- In Assassin’s Creed: Ascendance, the Papal Guard under Cesare were shown to wear the coat of arms of Pope Julius II, comprised of the Papal Keys and a shield with a golden oak tree on a blue field.
- During Juan Borgia's party, a Papal guard was tasked to deliver the debt money of Egidio Troche. He spoke with a British or German accent and used some German words.
- During the infiltration of the French headquarters in Rome, Ezio faced some Papal guards. Although the Borgia had already left the battle by this time, the guards were an indication of the close alliance between Cesare and Octavian de Valois.
- By Cesare Borgia's arrest in December 1503, the Borgia had lost all their power in Rome. However, when Cesare was arrested by Fabio Orsini and the Papal troops, they still carried the emblem of the Borgia, despite being commanded by the new Pope Julius II.
- Similarly, when Ezio infiltrated Belriguardo Castle in 1506, Papal guards that bore the Borgia emblem chased after him, even though Ezio was in Ferrara and the Borgia were no longer in power. Since a guard could be heard mentioning Pope Julius had lent the Duke some of his own troops, the oversight is again about the guards sporting the Borgia colors.
- The Templars overseeing the War Machines' construction were always Papal guards.
- There was an assassination contract named "Graduation", where Ezio had to kill four Papal guards training within the Castel Sant'Angelo.
- Papal guards were not commonly found in Rome, and appeared more often in main story memories. However, a group of four Papal guards was always stationed right outside the Castel Sant'Angelo in the Vaticano District, and these guards were always suspicious of Ezio, attacking on sight despite Ezio's notoriety level.
- Papal guards were not affected by Ezio's taunts.
- Cesare Borgia himself fought much like a Papal guard, and was able to dual-wield a pistol and sword as they did.
- The Papal guards were considerably stronger than Ezio and had a larger build, with all of them being at least a head taller than him.
- Smoke bombs had no effect on a Papal guard while engaged in combat. However, the bombs functioned as normal if the guard was taken by surprise.
- A Papal guard could only be disarmed if he carried a pistol.