Ed Wuncler III and Gin Rummy are based on George W. Bush and Donald Rumsfeld. Ed wears a medallion that says "W" which is Bush's nickname and "Rummy" is Rumsfeld's nickname. In the first episode, Ed Wuncler I says of his grandson, "In 30 years that boy will be the President of the United States... and he'll still be a fucking idiot."
Alicia Keys was originally cast as Huey. The producers wanted her to play Huey as well, but she refused. She originally read Huey's lines in the recording sessions just as a placeholder until another actor was cast. But the producers managed to convinced Regina King to take the role and she came up with a voice.
The music that plays when Uncle Ruckus appears is a variation of John Williams' "Jabba's Theme" from Star Wars: Episode VI - Return of the Jedi (1983).
The controversial nature of the comic strip (as well as Aaron McGruder's insistence on maintaining creative control) lead to several failed attempts to get this series going since 1999. McGruder initially developed "The Boondocks" as a television series before turning it into a strip. Some of the would-be homes of the series included Home Box Office (HBO) and Music Television (MTV). In 2003, the Fox Network ordered a pilot with the prospect of picking up the series. They eventually passed, only to have the series taken up by Adult Swim.