During the attack on Port Royal, Twigg and his companion, Koehler arrive in the prison and arriving there, the two confront Jack Sparrow and inadvertently revealed the true nature of how they have the curse, indicating that he and the other crewmen are immortal. Later onboard the Black Pearl, Twigg and the rest of the crew set sail for Isla de Muerta with Elizabeth Swann as the ship's prisoner. Later during the ritual, when it is found out that Elizabeth was not Bootstrap Bill Turner's daughter, the curse could not be broken and thus, Elizabeth's blood did not work. Twigg then blames Barbossa about Elizabeth's uselessness as Twigg joins the crew in searching for Elizabeth and the missing medallion.
During battle against the HMS Interceptor, Twigg fought against the motley crew who fired everything inside the Interceptor and during battle, Elizabeth was forced to walk the plank. He later fought against the HMS Dauntless and just like any cursed member, he has the ability to walk underwater and alongside the rest of the cursed crew, he prepared for an ambush on the ship. During the battle, Twigg and the rest of the cursed crew fought against the British Royal Navy where he fought against the marines in combat. With Barbossa defeated by Jack Sparrow and the curse broken, Twigg surrendered with the remaining cursed crew after the curse is broken and was later arrested by Norrington.
In the video game that is considered non-canonical to the film's universe, Twigg is one of the cursed pirate enemies in the Pirates of the Caribbean universe appearing as a generic enemy in the Port Royal hub.