Following on from Super Adventure Island, in this game Master Higgins, along with his wife Tina, are stricken by a storm while on their honeymoon. Both of them end up separated by the storm, and Master Higgins wakes up to find out that he does not remember anything. After exploring the island he is on, he finds out that the island is ruled by a king who recently found a girl that also suffers from amnesia and is appointed to become queen. However, she is mysteriously kidnapped and the king requests Higgins to find her. Higgins accepts the mission since he feels that the girl is able to help him recover his lost memories.

Super Adventure Island II puts the player in a world map that is separated in different islands. Each one has various items and equipment, some of which can be used to access other areas on other islands to progress.

On the world map, the player travels by raft on the sea. While on the map and like in some RPGs, an enemy can randomly attack, which changes the game in another perspective (in this case, a side-scroller), where the player must defeat the enemies or flee from the area by going to a side of said area.

Once the player accesses an island or some secret area, the game switches to a side-scrolling view. In this mode is where the main game takes place.