The show features the adventures of Scrooge and his great-nephews. The nephews, who were originally living with their uncle Donald, are left in Scrooge's care when the former joins the Navy.

Though Scrooge is the richest duck in the world, he constantly tries to find ways to increase his wealth. Many episodes involve protecting his wealth from villains who want to rob Scrooge of all his money. The prominent recurring antagonists in the show include the Beagle Boys and Magica De Spell who are always finding ways to rob and swindle Scrooge and his nephews. Scrooge's nemesis in the show is Flintheart Glomgold, who always tries to devise plans to dethrone Scrooge McDuck from his "Richest duck in the world" title.

The show's second season saw the addition of characters Fenton Crackshell and Bubba Duck. Along with them came stories that generally shifted away from the globetrotting plots of the first season, and revolved primarily in the contemporary setting of Duckburg. Episodes would feature either Bubba or Fenton but rarely both.

Although Scrooge and his nephews were the show's main characters, some episodes focused on other characters like Launchpad or Gyro.

Some episodes are based on Carl Barks stories or simply have elements from such stories. For example, the episode "The Unbreakable Bin" is based on Barks' story "The Unsafe Safe

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