Lufia II: Rise of the Sinistrals is a prequel to Lufia & the Fortress of Doom. Its events take place ninety-nine years prior to it, and it explains the origin of the series' antagonists, the group of super-humans known as the Sinistrals. The player controls the ancestor of the first game's protagonist, the swordsman Maxim. After having encountered a mysterious woman named Iris, Maxim goes on a journey to find other heroes who would help him to stop the Sinistrals from destroying the world.

Like the first game, Rise of the Sinistrals is a Japanese-style turn-based RPG with many puzzle elements thrown in. The game makes extensive use of puzzles in its dungeon layouts; various items and accessories must be used to solve them. It also features a "Capsule Monsters" system; monsters can be summoned to fight alongside the party in battles. They would evolve when fed weapons, armor, or special fruits. Unlike in the first game, there are no random battles in the dungeons: all the enemies are visibly moving on-screen.