Aaron McGruder was born in . When McGruder's father accepted a job with the National Transportation Safety Board, McGruder moved to at age six with his parents and his older brother. He attended a Jesuit school from grades seven to nine, followed by public high school at Oakland Mills High School and the University of Maryland, from which he graduated with a degree in African American Studies. The Boondocks debuted in the campus newspaper, The Diamondback, in late 1997, under its then-editor, Jayson Blair. McGruder created the comic while working at the Presentation Graphics Lab on campus. At the time, he was also a DJ on the "Soul Controllers Mix Show" on WMUC.

McGruder currently lives in , where his projects include the Boondocks animated series and the Super Deluxe variety comedy series, The Super Rumble Mix Show. He is the author of five Boondocks collections: All The Rage, Public Enemy #2, A Right To Be Hostile, Fresh for '01: You Suckaz, and Boondocks: Because I Know You Don't Read The Newspaper. McGruder is also the co-author, with Reginald Hudlin, of a 2004 graphic novel, Birth of a Nation: A Comic Novel, drawn by cartoonist Kyle Baker, and a frequent public speaker on political and cultural issues.

McGruder's strip has been a veritable lightning rod for criticism since it debuted in 1999, with newspapers consigning it to editorial sections, or dropping the strip altogether. Favored targets of The Boondocks include BET, Condoleezza Rice, Whitney Houston, Bill Cosby, Vivica A. Fox, black libertarian commentator Larry Elder, even Star Wars. One infamous strip immediately following the September 11, 2001 attacks involved Huey calling the FBI's terror tip line to report Ronald Reagan for funding terrorism. When a 2004 strip had Huey and Caesar handing out "Elder" awards for being embarrassments to black people, their namesake Larry Elder fired back with an opinion column in which he handed out "McGruders" for offensive comments uttered by black leaders.

During a keynote address at the July 12—14, 2002 H2K2 conference, McGruder connected the Bush administration to 9/11:

In 2003, McGruder accompanied California Rep. Barbara Lee on a controversial visit to Cuba, where they met Fidel Castro. Later that year during a reception hosted by The Nation, McGruder offended many attendees by defiantly recalling his support for Ralph Nader's 2000 presidential bid. McGruder had to endure heckling and walkouts as he defended his commitment to left-wing causes, including, he claimed, calling Condoleezza Rice a "mass-murderer" to her face during the 2002 NAACP image awards. In 2009, it was reported that McGruder had told a Martin Luther King Day audience at Indiana's Earlham College that then-President-elect Barack Obama was not black. McGruder claimed that he was misquoted, while maintaining he remains "cautiously pessimistic" about Obama's presidency.

A feud with Black Entertainment Television has given McGruder much material both for his strip and the animated series based upon it; he has had an adverse relationship with BET for years. Two episodes from Season 2 of The Boondocks animated series which depict BET negatively were not aired in the U.S. and Canada; however, they resurfaced weeks later and were included on the season DVD set.