As the Simpson Family; Homer, Marge, Bart, Lisa and Maggie, take a stroll through town, they encounter a jewelry store being robbed by Waylon Smithers, who bumps into Homer, leading a precious diamond he stole to land in Maggie's mouth. With Maggie using the diamond as a makeshift pacifier, Smithers takes Maggie with him, sending various goons to keep the Simpsons from following him. Fighting their way through various areas, such as Krustyland, Moe's Tavern and even a dream world, the Simpsons eventually arrive at the Springfield Nuclear Power Plant, where they face against not only Smithers, but also Mr. Burns, who attacks them in a plutonium-powered mech. After managing to defeat Burns, the Simpsons rescue Maggie and head back home, throwing the diamond away.

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The Simpsons is a side-scrolling beat 'em up for up to four players, with each one playing as a member of the Simpsons family: Marge, who swings her vacuum cleaner; Homer, who punches and kicks; Bart, who wields his skateboard; and Lisa, who attacks with a jump rope. Along with the standard array of jumping and attacking, two players can team up to form a joint attack, which differs depending on which characters are used. For example, Homer can lift Bart up to use him as a melee weapon, whilst teaming him up with Marge puts them into a powerful cartwheel attack. Players can also pick up food items to restore health, as well as objects they can throw at enemies and items that temporarily power up their attacks. Players are given a small number of lives, which are lost if the player's life bar runs out. If the player runs out of life with no lives remaining (represented by a Bart-like devil appearing before them), the player has 20 seconds to add credits or the game ends. At certain points in the game, players compete against each other in button-bashing minigames to earn additional points (computer controlled characters replace characters not being played by real people). Super fun!