He is voiced by the American actor, producer, and writer Seth Green and first appeared on television, along with the rest of the Griffin family, in the episode "Death Has a Shadow" on January 31, 1999.

Chris Griffin was created and designed by the series' creator, Seth MacFarlane, who was asked to pitch a pilot to the Fox Broadcasting Company.

The animated short film was created by Seth MacFarlane at the Rhode Island School of Design in 1995 which later led to the development of Family Guy, which aired three years later.

Seth Green has stated that his main inspiration for Chris' voice came from envisioning how the Buffalo Bill character from the thriller film The Silence of the Lambs would sound if he were speaking through a PA system at a McDonald's restaurant.

On the Volume 1 DVD Boxset TV guides special Family Guy edition, it is stated that Chris "wouldn't hurt a fly, unless it landed on his hot dog".

In one episode, he thinks he got a bad grade on his geometry test when he tickled his brain with a plastic army man's rifle inserted into his nose, accidentally puncturing a lobe.

He also shares his father's cartoonish lack of common sense, tends to be absent-minded, gets confused easily, and appears to be extremely naïve; in "Lethal Weapons", when Peter and Lois are having a fist fight, Chris cheers for the former, telling him to "kick her ass!".

As the series progresses and Meg is seen more often with her group of friends, Chris's social status is greatly reduced to the point of being unpopular and virtually friendless at James Woods Regional High School.

Connie and Meg then briefly team up to humiliate Chris by having Neil Goldman show the school a video of him re-enacting a scene from The Silence of the Lambs in which Buffalo Bill dances nude in front of a mirror, which results in Connie regaining her popularity, while Chris is socially demoted back to being an outcast.

In a 2003 interview, Seth MacFarlane stated that the writers thought it would be funny to give Chris a childhood fear that is actually real, since he has "a childlike mind".

This gag is continued in "Something, Something, Something, Dark Side": though Chris attempts to maintain a cool head, he storms off again when Peter offers to tell the story of Without a Paddle, a critically panned film that featured Green.

Outside of the Star Wars-themed episodes, "Road to the Multiverse" plays on the running gag, but with Stewie provoking the Robot Chicken universe counterpart of Chris by asking "How does it feel to be on a major network for thirty seconds?