Jesus has a special relationship with Santa Claus, since they are both considered icons of Christmas time. Their relationship is often characterized by friction, but they usually reconcile in the end.
In The Spirit of Christmas: Jesus vs. Santa, the pair fought in order to decide what Christmas was really about. However, they reconciled by the end of the short after Brian Boitano imparts his wisdom upon them.
They also sing a duet in "Mr. Hankey's Christmas Classics". However, partway through the performance, Santa gets upset because, "There's, like, 300 Jesus Christmas songs and only four fucking Santa ones!" However, they again reconcile by the end of their performance, and join each other in singing "White Christmas".
In "Red Sleigh Down", Jesus helps the boys on a high-risk mission to rescue Santa Claus from the Iraqis, who shot him down over their airspace and are torturing him. However, the rescue mission goes awry, and Jesus dies during the mission, sacrificing himself to save Santa. At the end of the episode, Santa dedicates Christmas to the memory of Jesus.
The boys, Stan Marsh, Kyle Broflovski, Kenny McCormick and Eric Cartman, have met and cooperated with Jesus on numerous occasions. In The Spirit of Christmas: Jesus vs. Santa, they help him find the mall and later tell both Jesus and Santa that the point of Christmas is to get along rather than fight.
In "Red Sleigh Down", Jesus joined the boys on the rescue mission to Iraq to save Santa Claus. Kyle killed Jesus in "Fantastic Easter Special", but only at the latter's behest, in order to escape from their imprisonment. Kyle was extremely reluctant, and after Jesus' violent death, he looked pretty traumatized.
Jesus is depicted as the leader of the "Super Best Friends" with several other religious figures, including Muhammad, Buddha, Krishna, Joseph Smith, Lao Tse, and Moses and's also Seaman who isn't a religious figure of any sort, but is an ineffectual superhero that is the butt of jokes from the other heroes. The group prevents the Blaintologists from committing ritual suicide in "Super Best Friends", and also work together in "200" and "201" to stop Mecha-Streisand.
- The Spirit of Christmas - Fights Santa and Frosty.
- "Big Gay Al's Big Gay Boat Ride" - At Stan's football game, responds to Jimbo.
- "An Elephant Makes Love to a Pig" - Mutant Stan breaks through his set.
- "Death" - Stan calls him to ask about assisted suicide.
- "Mr. Hankey, the Christmas Poo" - Jesus is alone at his birthday party.
- "Damien" - He competes in a boxing match with Satan, which he wins.
- "Mecha-Streisand" - Jesus proclaims Robert Smith his savior.
- "Cartman's Mom is a Dirty Slut" - Along with Father Maxi, he had an affair with Liane Cartman. But he wasn't seen as one of Eric's potential fathers.
- "Chickenlover" - He was driving the car with Stan, Kyle and Officer Barbrady.
- "The Mexican Staring Frog of Southern Sri Lanka" - Jesus has to revamp his show, Jesus and Pals, to compete with rival show Huntin' and Killin'.
- "Spontaneous Combustion" - Jesus talks about global warming on his show.
- South Park: Bigger, Longer & Uncut - Appears for a moment as one of the American troops marching outside Kyle's house, wearing an army uniform but without a helmet to make room for his halo. He also seen in the military base and finally seen at the back of the crowd singing at the end of the film.
- "Mr. Hankey's Christmas Classics" - Sings a duet with Santa.
- "Are You There God? It's Me, Jesus" - Provides entertainment for the new millennium.
- "Probably" - Tells the boys to go to school instead of church.
- "Fat Camp" - Kenny is a guest on his last Jesus and Pals show.
- "A Very Crappy Christmas" - Star of the boy's Christmas card.
- "Super Best Friends" - Leader of the Super Best Friends.
- "Red Sleigh Down" - Goes to Iraq with the boys, and dies on a mission to rescue Santa Claus.
- "The Passion of the Jew" - Kyle goes to see the movie, The Passion of the Christ, where Jews are depicted as nasty people torturing Jesus, making Kyle feel guilty for being Jewish.
- "Fantastic Easter Special" - Stopped Bill Donohue from becoming the Pope.
- "Imaginationland, Episode II" - One of the Council of Nine.
- "Imaginationland, Episode III" - One of the Council of Nine.
- "200" - The leader of the Super Best Friends.
- "201" - Appears again as the leader of the Super Best Friends.
- "Butterballs" - Appears in the producer's bathroom and bullies him by threatening him with Hell.
- "A Scause For Applause" - Center of a scandal, stating that his miracles were influenced by performance enhancing drugs.
Jesus appears in the Stick of Truth as a summonable character in battles. In order to use Him, Priest Maxi sends you to find Jesus in the church, where he's hiding, and he tells you that finding him the next time won't be so easy. The second time you find Jesus, he's hiding behind the podium and you have to turn off the lights and focus the spotlights on the podium, revealing his shadow. You then unlock him as a summon and get him and Priest Maxi as friends