Christopher Cross "Chris" Griffin is the middle child of the Griffin family. He is 13 in the first three seasons, and declared 14 in "Trading Places". He celebrates an unspecified birthday in "Follow the Money".
Angry at the family during the 'recording' of a DVD commentary in "You Can't Handle the Booth!", Lois speculates that Hoffman may be Chris' real father, having slept with him during the filming of Twister nine months before Chris was born.
Chris is voiced by Seth Green. However, he had not been hired until after the original Pilot Pitch. For that, series creator Seth MacFarlane provided Chris' voice, giving his voice a deeper tone as compared to how Green does it.
Though Chris is not the brightest one in the family, he is particularly coherent and makes a good point when talking about movies with Carl. Chris deals with the problems that most pubescent boys face: acne, girls, and school. Chris has been known to feel self-conscious about himself, especially his weight. He was referred to as an "Elephant Child" when he was born. Chris is also willing to do something as drastic as to convert to Judaism order to do better in school, specifically math in "When You Wish Upon a Weinstein". However, in "Family Goy", he would find out that he was already Jewish. He once believed his low grades in mathematics were caused by himself when he tickled his brain by sticking an army man's rifle into his nose and accidentally puncturing a lobe. Chris both enjoys and excels at drawing and once almost managed to become a famous artist in New York, but failed when he refused to estrange his family in "A Picture's Worth a Thousand Bucks".
Chris, like his father, is obese, has a low IQ, and little to no common sense; however in "Fast Times at Buddy Cianci Jr. High" Brian refers to Chris' class as intelligent before going to teach remedial English. Also, various story lines such as "Movin' Out (Brian's Song)", give him autistic savant talents, such as artistic ability, and detailed knowledge of film and TV actors. Both he and Peter have also demonstrated proficiency in the use of American Sign Language. Occasionally he exhibits unexpected, uncharacteristic insights, such as when he gives Peter and Lois a detailed and articulate lecture on the effects and disadvantages of marijuana. He has also demonstrated an ability to quickly adapt to new cultural surroundings. For example, when the family moved to London, England in "Patriot Games", Chris was the only member of the family who was able to quickly learn and speak cockney English.
Chris is usually depicted as naive to the point of blamelessness. However, when Peter and Lois were having a fight in "Lethal Weapons", Chris cheered for Peter, telling him to "kick her ass!" Also, in Stewie Griffin: The Untold Story, when Lois and Peter are trying to make out, the children mistake it for a fight and Chris says "I don't know what they're fighting about, but I think Dad's winning. Go Dad!"
In "Emission Impossible", it is revealed that Chris was born as an accident, due to a broken condom. As a result, Peter and Lois filed a lawsuit against the company and bought the house they currently live in. In "Peter's Daughter", Lois revealed that she smoked and drank a lot when she was pregnant with Chris to try and incite a miscarriage, but chickened out halfway through the pregnancy. This may be the explanation for Chris' lack of intelligence and other anomalies. Also, it is known in "And the Wiener is..." that Chris possesses an abnormally large penis.
Chris is generally mild-mannered and friendly, but is often rude to others when angered, such as in "Long John Peter", when he both insulted Joe Swanson for his handicapped status, and hit Brian with a chair just to go back to the vet and see a girl who broke up with him. Another example was in "Movin' Out (Brian's Song)", when Brian just came back after being dumped by Jillian, Chris said, "Welcome home, asshole!"
Chris has the closest relationship with his father Peter Griffin. However, in "The Son Also Draws" and "If I'm Dyin', I'm Lyin'" he seems a bit afraid that he doesn't live up to his father's expectations. He and Peter enjoy competing, even though Chris almost always loses to his dad. In "He's Too Sexy for His Fat", Chris seems more upset with his father than other episodes, due to Peter getting much more physically fit compared to the fat Chris. In a few episodes including those listed above, Peter does seem disappointed or ignorant to Chris.
Chris seems attracted to his own mother in several episodes. In Stewie Griffin: The Untold Story, he even seems turned on to a lesbian conversation his mother has with him. In "E. Peterbus Unum", he also passes Meg a note in their home school that he thinks "Mrs. Griffin" is hot and in "Model Misbehavior" where he says that he'll masturbate to pictures of her. In "Bigfat", he kissed Lois, declaring that he didn't want to live by society's rules. He once dated a girl named Lindsey who was a dead ringer for Lois in "Tom Tucker: The Man and His Dream". He explained that as Lois puts up with Peter's stupidity all the time, Chris thought the only person who could love him would be someone like his own mother.
Chris has a normal sibling rivalry with his older sister Meg, which Peter and Lois often get frequently annoyed of. When the family starts to fight in "Lethal Weapons", Meg and Chris tackle each other. In "Stew-Roids", Meg conspires to take him down when he starts dating a popular girl. However, when he becomes concerned for Meg's safety in "Saturated Fat Guy", he allows himself to be injured to protect her. In "Hannah Banana", Meg reveals that she and Chris practice kissing with each other. But later in "Halloween on Spooner Street", Meg and Chris become repulsed when they accidentally make out in a closet at a Halloween party. In "Fresh Heir" she walks into Chris' room wearing a towel to announce their bath together, only to find Peter cleaning the room. Natalia finds the pair kissing in "Nanny Goats".
Chris seems to be the only member of the family besides Brian who is completely aware of Stewie being an evil genius. Despite this, Chris seems to enjoy Stewie's company, although he is often the guinea pig to Stewie's experiments such as in "The Story on Page One", although he usually doesn't know it.
Chris is often shown to be hostile toward Brian. in "North by North Quahog", he even yells at Brian and tells him that he has no soul which seems to upset Brian. In "Fast Times at Buddy Cianci Jr. High", he gets angry at Brian who is at the time, his substitute teacher for giving him an "F", then eggs his house with Peter despite the fact that they live together. In "Untitled Griffin Family History", he yells out that he hates Brian, and in "Movin' Out (Brian's Song)", he openly calls Brian an "Asshole" for no reason other than to make fun of him with the other members of the family. In "Long John Peter", he also hits Brian with a chair which gives Brian two black eyes, several broken bones, and bends his nose to the right just so he can bring him to the vet to see his ex-girlfriend. Although he seems to care a bit for Brian.
While possessing incomplete-at-best sexual knowledge, Chris nevertheless has a decent understanding of sex and masturbates frequently like most boys his age. In "Love Thy Trophy", Chris is convinced babies come from the Child Welfare Office.
In several episodes, he demonstrates a compelling interest in girls such as in "To Love and Die in Dixie", Chris shows a romantic interest in a girl named Barbara. Later in the episode when he and his family are exiled to the South, he meets and befriends a person named Sam, who later kisses him despite being a boy. Confused about the kiss, he confronts Sam, who's revealed to be a girl dressed in guy clothes. After talking to Sam, Chris feels opened enough to express his feelings for her. He felt nervous about talking to her, she suggested to him that he should pretend she was a male, and Chris happily agrees to making out. In "You May Now Kiss the...Uh...Guy Who Receives", he is attracted to a student named Alyssa, who is a young Republican. Chris becomes a Young Republican because Alyssa offers to let him touch her breasts. In "Jungle Love", Chris runs away to South America to escape the bullying at school and joins the Peace Corps. He gets the entire tribe, whom he's staying with, to dance. By doing this Chris married the Chief's daughter, Loka although he had to leave her behind at the insistence of his parents and after he reveals himself to be a freshman in high school. In "Long John Peter" Chris falls in love with a vet intern named Anna, who he asks out. Their relationship goes well until Chris follows Peter's advice to put her down on a date to make progress, but Anna breaks up with him instead. At the end of the episode, they kiss and get back together. After being sent to Italy by Peter in "La Famiglia Guy", Chris meets and eventually marries Tammy, but their marriage is cut short when she is killed by a car bomb.
He is often harassed by his neighbor, Herbert, an elderly pedohebephile . However, Chris always seems to evade Herbert's advances. In "Play It Again, Brian", Chris finally confronts Herbert by blatantly asking him "Are you a pedophile?"
Chris also comments openly about masturbation in several gags in "Running Mates", "The Fat Guy Strangler" and "Barely Legal". However, in "Holy Crap", grandfather Francis Griffin accuses Chris of masturbating when he was really just defecating by telling him that was he was doing in the bathroom was morally wrong and God can see it. He spends the rest of the episode holding in his waste until Peter lets him "defy" his grandfather.
Connie DiMico, a girl Meg's age, who is the self-described "most popular girl" at James Woods Regional High School, asks Chris out in "Stew-Roids". She does so under the premise that she had already exhausted her dating relationships with all the popular boys and now, left with just the "unpopular" boys, promises to convert him into a suave, popular student. Connie had intended the relationship to be temporary, but she and Chris quickly hit it off and become a serious couple. At a party at the Griffins' house that weekend, Chris breaks off the relationship, having found interest in two other girls he had been kissing and unwittingly teaching Connie a lesson in dating others simply to further her own status.
- Chris' full name, Christopher Cross Griffin, is an homage to the singer-songwriter who goes by the same name.
- Chris' voice is inspired by Ted Levine's Buffalo Bill character in The Silence of the Lambs. 
- Chris originally wore a gold hoop earring in his left ear. Due to the Korean animators flipping of the drawings, the earring would appear on both sides, leading to it being dropped from Chris' design.
- Chris' birthday is February 8th as according to "German Guy", which is also Seth Green's birthday.
- Chris is the only blond in the Griffin Family.
- In The Cleveland Show episode "Our Gang" Chris appears in a gag in which he falls through the ceiling of Cleveland's house.
- According to Lois in "Emission Impossible", she and Peter were using a condom the night he was conceived, but it broke, they were also able to sue the company, which got them their house.
- When Joe starts to look for new friends after Peter, Mort and Quagmire burn down Goldman's Pharmacy in "Burning Down the Bayit", Peter notes the Chris is a bit scared of Joe as he thinks of him as a Transformer that broke halfway through.
- In "Fresh Heir", Chris has become the sole heir to the Pewterschmidt fortune.
- In "Baby Got Black", Chris dates Jerome's daughter, Pam.
- A TBS Facebook promo in celebration of the upcoming 2017 My Little Pony feature film depicts him as a Brony. 
- Peter claims that Chris has Crohn's Disease in "Underage Peter".
- Chris is revealed to have had a stillborn twin that Lois planned to name "Tmas" in "Don't Be a Dickens At Christmas".
- He claims in "Switch the Flip" that he weighs 215 pounds, although Brian estimates it at 230.
- Despite previous evidence of Chris' birth such as the 'elephant child' photo in "He's Too Sexy for His Fat", Peter mentions finding Lois' gun with Chris' adoption papers in "Regarding Carter".