As in the movie version, Peter Quill aka Star-Lord listens to classic rock on his Walkman (and occasionally a song is played in an episode), each episode title is a plot-related pun from a classic 70s or 80s rock song: e.g., "Take the Milano and Run" is from the Steve Miller Band hit "Take the Money and Run".

A series of one-shots were released prior to the series premiere detailing the origins of several characters and events that occurred prior to Guardians of the Galaxy (2014).

Takes place in the same universe as Ultimate Spider-Man (2012), Avengers Assemble (2013) and Hulk and the Agents of S.M.A.S.H. (2013), designated Earth-12041 which is also known as Marvel Animated Universe.

Many of the cast in Guardians are past "Transformers" voice actors: Will Friedle (Star-Lord) appeared in Transformers Prime (2010) & Transformers: Robots in Disguise (2014) David Sobolov (Drax) appeared in Beast Wars: Transformers (1996) & Transformers Prime (2010). Trevor Devall (Rocket Raccoon) had starred as Alpha Q in Transformers: Energon (2004) Kevin Michael Richardson (Groot) appeared in Transformers: Revenge of the Fallen (2009), Transformers: Animated (2007), Transformers Prime (2010), and Transformers: Robots in Disguise (2014). Jeff Bennett (Rhomann Dey) appeared in Transformers: Animated (2007). and Cree Summer (Nebula) played Blackarachnia in Transformers: Animated (2007)

Is not part of the Marvel Cinematic Universe.

Many of the cast are past "Star Wars" voice actors: Trevor Devall voices Palpatine in the Lego Star Wars franchise. Vanessa Marshall voices Hera Syndulla in Star Wars: Rebels (2014) . James Arnold Taylor voices Obi-Wan Kenobi in various Star Wars media. Kevin Michael Richardson voiced Jabba the Hutt in Star Wars: The Clone Wars (2008). Jeff Bennett voiced Darth Revan in Star Wars: The old Republic (2011). Cree Summer voiced Luminara Unduli in Star Wars: Clone Wars (2003). -Dave Fennoy voiced General Krell in Star Wars: The Clone Wars (2008).

The series will take place after the film of the same name however director James Gunn claims the series isn't official MCU canon. The series will share several nods to the feature film and several references to the Marvel Cinematic Universe such as the presence of Thanos and Loki, a resurrected Ronan the Accuser and the return of the Collector. The mystery of Peter Quill's past will be explored in the series while his father's identity will still remain hidden, as he will soon be revealed in Guardians of the Galaxy Vol. 2 (2017).

Peter Quill learns he's part Spartax. In the comics, he's the son of J'son of Spartax, Emperor of the Spartoi Empire.