While battling his nemesis, the evil pirate LeChuck, Guybrush accidentally unleashes an insidious voodoo pox that threatens to transform the buccaneers of the Caribbean into unruly pirate monsters. Players will experience the humor, romance, and swashbuckling action the Monkey Island games are famous for and unravel an insidious plot which is revealed across the course of the series.

The game's twisty plot leads hero, Guybrush Threepwood, on a hilarious quest throughout the fabled Monkey Island. Tales of pirate wealth attract Guybrush, who lands at the port of Mêlée with high hopes, no money and an insatiable desire to become a pirate. If the player is clever enough, Guybrush will win the confidence of Mêlée's established pirates and soon find himself blown by the winds of fate toward Monkey Island -- a storied isle whose name alone chills the bones of even the most bloodthirsty buccaneers.