While stripping the evil pirate LeChuck of his demonic mojo, Guybrush Threepwood accidentally infects the Caribbean with the expelled voodoo. The resulting curse threatens to turn buccaneers into unruly pirate monsters.

Pursued by a notorious pirate hunter and a creepy French physician who believes Guybrush’s infected hand holds the secret of eternal life, he sails the seven seas in search of La Esponja Grande, a legendary sea sponge with powerful voodoo-cleansing abilities.

As the quest unfolds, it becomes part of a larger and more sinister plot, and good and evil are not always as they seem. The story builds toward an unexpected finale in a modern point-and-click adventure.