In this era, Romagna was largely dominated by marshes, wetlands, and a number of scattered buildings. It also housed the Forlì docks, where ships from other areas stationed in its ports. Civilians could often be seen fishing from the wharves, or selling fish from market stalls nearby.
In 1480, Ezio Auditore rode into the area, after being chased through the Appennine Mountains by Borgia soldiers. He traveled through Romagna to access a ferry, up the coast of the Adriatic Sea to Venice, alongside his close friend Leonardo da Vinci. Initially he was held up due to his lack of paperwork, though Caterina Sforza, Countess of Forlì, solved this problem when she took a shine to Ezio, following him rescuing her from an isolated rock on the Forlì docks.
In 1488, after recovering the Apple of Eden, Ezio and his uncle Mario Auditore decided to take the artifact to Forlì, where they met with Caterina in the wetlands outside the city. However, upon reaching Forlì, word spread that the forces of Checco and Ludovico Orsi had invaded and gained control of the majority of the city.
After discovering that the gates to the city were locked, Caterina instructed Ezio to infiltrate it via a secret entrance, which involved Ezio swimming under Forlì's moat and entering from there. While Caterina distracted the invaders with a volley of insults, Ezio dispatched any soldiers in his way and opened the gates to the city, allowing Caterina and her soldiers inside, where they swiftly retook it.
On entering Forlì, Ezio, Caterina and Niccolò Machiavelli made their way to the Rocca di Ravaldino to fight off the attacking invaders, defeating them and reaching the inner citadel. However, upon reaching it, Caterina discovered that her children, Bianca and Ottaviano Riario, were missing and that the Orsi brothers and their army of Borgia soldiers had begun breaching the citadel, forcing Ezio and the Assassins to defend. Despite this, they were able to successfully fend off most of the attackers and hold the city, though they were soon confronted by the Orsi brothers themselves.
The two called out to Caterina, informing her that they had kidnapped her two children, explaining that they would only be returned once Caterina had handed over her husband's map detailing the locations of the Codex pages. In response, Caterina vehemently hurled insults at them, refusing to hand over the map. The Orsi brothers stated in return that she had one hour to hand over the map before they killed her children. On their departure, Caterina turned to Ezio for help, asking him to rescue her children for her. To this, Ezio agreed, and handed over the Apple to her to protect.
Ezio departed and headed for the Romagna countryside, where he defeated the guards imprisoning Bianca, who then directed him to the location of her brother, Ottaviano. From there, he headed through the marshes to a nearby lighthouse, where he scaled the building, killed Ludovico and rescued Ottaviano. However, upon dispatching Ludovico, Ezio learnt that the captured siblings had been a distraction, allowing for the theft of the Apple. With this, the Assassin hurried back to the city, discovering that Checco had acquired the Apple.
Ezio tracked him down and killed the last Orsi brother and retrieved the Apple, though not before Checco managed to stab Ezio in the abdomen, causing him to lose consciousness and drop the artifact. As Ezio slipped into unconsciousness, he saw a black-robed monk with a missing finger pick up the Apple and walk away.
Afterwards, Ezio awoke inside the city, where he was being tended to by Caterina, after Forlì guards discovered him in the countryside whilst scouting the area. Upon regaining consciousness, Ezio explained to Caterina what had happened, and she pointed him in the direction of a nearby abbey in the wetlands outside the city as a good spot to look for clues, regarding the location of the mysterious black-robed monk. Additionally, Caterina gave Ezio the Codex map, to which he thanked her and left, with the abbey as his objective.
Ezio traveled through the Romagna marshlands until he reached the abbey, where he saved an Irish priest, Brother O'Callahan, from Borgia thugs. Ezio questioned him about the monk with a missing finger, and O'Callahan directed him to an abbey inside the city of Forlì.
The Assassin returned to the city and headed for the abbey, however, once he arrived there, one of the priests recognized him as the murderer of Stefano da Bagnone, the Templar that Ezio had assassinated nine years earlier. Fearful, the priest attempted to run away, though Ezio caught up to him and tackled him. He quickly explained that Stefano's death was necessary, and managed to convince the priest of this, before he inquired about the identity of the black-robed monk with the missing finger, which the priest confirmed to be Girolamo Savonarola. From there, Ezio asked where he might have gone, and the monk said that he may have returned to Florence, to which the Assassin quickly departed for.
- Before the release of Assassin's Creed II, developer Ubisoft Montreal referred to the area as the "Wetlands."
- Romagna was the poorest region in Assassin's Creed II, and its surrounding area was flooded with dirty water, ravaged buildings and overgrown with weeds. Very few civilians wore affluent clothing (such as feather hats and scarfs), nor did they possess a respectable amount of money to pickpocket.
- The Wetland Ebony and Wetland Ivory dyes for Ezio's robes were obtainable in Romagna from any tailor, and granted the "Perfect Harmony" achievement when worn together.
- Romagna was the location of the first Assassin's Creed II DLC, the Battle of Forlì.
- By downloading the additional Battle of Forlì content, the Flying Machine was available to access at any time, on top of a lighthouse, where a feather was also located.