The Simpsons is basically a side-scrolling beat-em-up featuring the characters from The Simpsons TV show. The player can choose to play as each of the four Simpson characters. Homer, who punches and kicks; Marge, who swings her vacuum cleaner; Bart, who wields his skateboard; and Lisa, who uses a jump rope as a whip. Other weapons such as hammers and bowling balls are also available to use.

The game's levels are Downtown Springfield, Krustyland, Springfield Discount Cemetery, Moe's Tavern, Springfield Gorge, Dreamland, the Channel 6 studio, and the Power Plant. Each level ends with a boss whose speed and strength will increase after taking a certain amount of damage.

Between levels, the player can compete against the other characters in two mini-games to be first to complete a task (inflating a balloon and waking up their character).

Waylon Smithers has just stolen a diamond from Springfield Jewelers for Mr. Burns. While trying to make a getaway, he crashes into Homer, which knocks the diamond out of his hand. Maggie catches it in her mouth, prompting Smithers to grab her and run off. The Simpsons decide to go after him, but Mr. Burns has tons of henchmen, who want to prevent the family getting their daughter back.