The musical number, "The Worry Song" with Stewie and a live-action Gene Kelly is an edited scene from the film Anchors Aweigh (1945). The sequence originally involved Jerry Mouse of Tom and Jerry fame. Stewie’s reflection in the floor remains that of Jerry.
At the end of the opening credits, there is a shot of Brian riding a horse and Stewie dressed up in an American flag shirt and wearing a mustache, a reference to the film Borat! Cultural Learnings of America for Make Benefit Glorious Nation of Kazakhstan.
Aspen was the destination of the main characters in Dumb and Dumber, who also lived in Rhode Island. Incidentally, during the opening credits, two slides have a resemblance to scenes from the film: a picture of Brian and Stewie riding a mini scooter, and Stewie with his tongue stuck to the metal of a chairlift pylon.
Stewie’s fantasy of Rupert’s funeral is a parody of Spock’s funeral in Star Trek II: The Wrath of Khan, right down to the music “Amazing Grace” being played on bagpipes.
After Peter crashes his car during his first car-jumping stunt, he refers to Matthew Broderick's car accident in Northern Ireland in 1987 in which 2 people died.
During the My Black Son intro, almost all of the shots are scenes from open themes of 1980s sitcoms. For example, when Peter and his black son, purportedly Emmanuel Lewis, are biking along a beach and get distracted by a thin black-haired woman, causing them to fall onto the sand, this is a parody of the John Ritter as Jack Tripper scene during the theme song of the first three seasons of Three's Company.
Also during the My Black Son intro there are nods to Punky Brewster when Peter picks up the frozen dinner, Family Ties with Peter in the Ohio shirt, Perfect Strangers with the revolving door, Who’s the Boss? with the curtain-vacuuming, Laverne & Shirley with the glove on the conveyor belt, the doors hitting each other, and the dough landing on Peter and Lois while they kiss, and Bosom Buddies with catching fruit with the bag.
When Lois opens the refrigerator and tells Peter to get out, he replies, “There is no Peter, only Zuul.” This is a reference to two scenes from the film Ghostbusters.
When Stewie and Brian are crossing into Colorado, the welcome sign says “Welcome to Colorado. More than just Kobe and Columbine,” referring to Kobe Bryant's rape case and a school massacre by two student gunmen at Columbine High School that happened near Littleton, Colorado.
When Stewie and Brian’s helicopter crashes, Stewie appears momentarily as the devil, just as John Candy appeared to Steve Martin in Planes, Trains & Automobiles while they were driving the wrong direction on the expressway.
In a montage scene with Meg and Peter, The Flintstones opening is parodied with Meg pulling into a drive-in movie, in which Peter sticks his head out through the roof of the car and Meg placing baby Pebbles and Bamm-Bamm on his head.
Peter says Meg is cooler than the other side of the pillow. This is a reference to ESPN sports commentator Stuart Scott, to whom the phrase has been attributed.
The scene where Peter strikes a series of mailboxes and eventually Mort Goldman with a baseball bat while leaning out a moving car window is similar to the scene in Stand By Me where Ace’s gang plays “Mailbox Baseball”.
The scene where Brian and Stewie pull a man out of his car through the broken window while yelling expletives is a reference to a similar scene from Reservoir Dogs where the character Mr. Pink, played by Steve Buscemi, running from a heist gone wrong, stops a car at a street corner, breaks the driver’s window and pulls the woman driver out of the driver’s seat and drives off with it, but not before tagging a few cops at the corner of the street.
When Stewie tells Stanford that Brian will lick peanut butter off any part of his body, Stanford pauses momentarily before saying, “Well I did go to Choate,” referring to Choate Rosemary Hall, a New England prepatory school.
The ski race towards the end between Stewie and the father who bought Rupert is a reference to the climax of Better Off Dead.
The sequence where Peter and Meg are talking right before Peter gets his license back is a parody of the ending sequences in Full House.
After Brian and Stewie carjack someone, a road sign says there are 2112 miles back to Rhode Island, a reference to the breakthrough album of rock group Rush.