Tales of Monkey Island: The Siege of Spinner Cay starts off just after the last chapter, where Guybrush has escaped Flotsam Island and has returned to the last place he saw Elaine. But when Guybrush spied Elaine, he saw her being consoled by a now human LaChuck. All ready to go after his wife, Guybrush got interrupted by a mercenary hired by The Marquis de Singe to bring back his cursed hand, and of course, by the time you finish dealing with this mercenary, Morgan LeFlay, Elaine and LaChuck are gone again. But at least you learn that they are on a nearby cluster of islands and that is where a majority of this episode's adventure takes place.
Guybrush reconnects with Elaine, but learns that the island's inhabitants, a race of merpeople, are in the middle of an argument with a pox-ridden pirate by the name of Captain McGillicutty. It seems that Guybrush isn't the only one who knows that La Esponja Grande is the only thing that can stop this disease, and McGillicutty is trying to convince the inhabitants to give him the three golden idols that are used to summon the creatures that can guide people to La Esponja Grande. So, as you might guess, Guybrush's adventure this time is to find said idols before McGillicutty can and summon the creatures so he can find La Esponja Grande and save the pirates.
Along the way, Guybrush will have to use several items he got from Flotsam Island like his Pyrite Parrot, or the tool used to activate ancient machinery (which we learn was made by the merpeople). He will have to trade insults with McGillicutty, at the cost of the Screaming Narwal's mast unfortunately and, even work hand in hook (LeFlay succeeds in taking Guybrush's cursed hand, you see) with LaChuck, even though he doesn't trust the former zombie-pirate and thinks he might be up to his old tricks and trying to steel Elaine from him.