At the beginning of the special, Charlie Brown, Linus, Sally, and a girl named Janice Emmons — a new friend and classmate of Charlie Brown and Linus — are seen waiting for the school bus. Once the bus arrives, Snoopy gets on casually, only to get kicked off. Sally, after hearing her brother remind Snoopy that dogs aren't allowed on the bus, simply says "Woof." to try getting out of having to get on, only for her brother to order her on.
While getting on the bus, Janice accidentally hits her arm on the bus railing, causing it to bruise. Linus notices that Janice bruises easily, and she mentions that she never used to. When they arrive at school, Janice starts feeling so ill that she has to go home sick. Three days later, her classmates discover that she is in the hospital.
After school, Linus and Charlie Brown decide to visit Janice in the hospital, where she tells them that she has leukemia. Charlie Brown asks if Janice is going to die, which upsets Linus for a moment, but Janice assures them otherwise. She explains what tests the doctors did to discover that she had leukemia and explains that while some of the tests were painful, not all of them were. She then shows them her IV line and explains her chemotherapy. Janice expresses her determination to recover from her illness, vowing to return to school and play on its swings once again. The news of his friend's illness hits Linus especially hard, and when he and Charlie Brown leave the hospital, Linus turns to him and asks, "Why, Charlie Brown, why?". He then goes home feeling sad and angry for what happened to Janice.
Once at home, Linus tells his sister Lucy about Janice's illness. Lucy at first does not seem to care, but when Linus mentions that he touched Janice's forehead when she felt ill at school, Lucy is immediately worried that Janice's illness might be contagious. Linus explains that cancer is not contagious, but then Lucy makes a rude remark about Janice, saying that she got the illness for being "a creepy kid". Linus, annoyed, explains to Lucy that Janice did not get the illness for doing something wrong. Lucy, however, refuses to change her ignorant (but fittingly childlike) attitude towards Janice's condition, and demands that Linus take back the glass of milk he handed her earlier, fearing that he might be transmitting the illness. Linus gets back at Lucy by refusing to accept the milk, so as not to get her "crabbiness".
Sometime later, Janice comes back to school, wearing a cap to cover her bald head, as she has lost her hair because of the chemotherapy. This attracts the attention of a schoolyard bully, who makes fun of Janice's baldness until an enraged Linus explains that she has cancer and asks the other boy if he would like to go through what she has gone through. The bully quickly softens and apologizes.
As Christmas approaches, Linus goes to Janice's house to give her a present, but her sisters inform Linus that she is at the hospital again, receiving treatment. One of the sisters complains about the attention Janice has been receiving, but later admits she and her other sister feel excluded due to Janice's illness. Linus gives her the present and leaves.
By the beginning of spring, Janice returns from the hospital and tells Linus she has a surprise for him, and she reveals the surprise at the end of the special while playing on the swings: her long blonde hair has grown back even longer than it was before, marking the end of her chemotherapy and her apparent recovery and presumed remission from the illness. As the credits roll, her cap falls to the ground, and Janice laughs one last time.
- Brandon Stewart – Linus van Pelt
- Olivia Burnette – Janice Emmons
- Kaleb Henley – Charlie Brown
- Jennifer Banko – Lucy van Pelt
- Adrienne Stiefel – Sally Brown
- Dion Zamora – Bully
- Brittany Thornton – Janice's younger sister (who resembles Frieda)
- Lindsay Sloane – Janice's older sister (who resembles Patty)
- Bill Melendez – Snoopy/Woodstock
- The book adaptation of this special is entirely illustrated by Charles Schulz himself, something he had not done for an animation adaptation since Charlie Brown's All-Stars.
- In the hospital, a non-tromboning adult voice is briefly heard over a PA. The voice says "Dr. Taylor to admitting," "Dr. Melendez to emergency," "Dr. Jaimes to Radiology," "Dr. Brown to pediatrics," and "Dr. McCann to ICU." Four of those names are derived from Warren Taylor, Bill Melendez, Sam Jaimes, and Chuck McCann, respectively.
- This is the only special in the franchise where Linus' security blanket is never seen or mentioned. This is most likely due to the seriousness of this cartoon.
- This is the second special to depict Linus liking a girl who likes him back, following Someday You'll Find Her, Charlie Brown.
- The scene where Linus walks home from the hospital is accompanied by a brief rendition of the American religious hymn "Farther Along", a song that, fittingly with the scene, is about a person who wonders why bad things happen to good people. The rendition of "Farther Along" is sung by Becky Reardon, who also sang "Alone" for Someday You'll Find Her, Charlie Brown.
- Janice's sisters resemble Frieda and Patty (although this does not hold true for Schulz's depiction of them in the book adaptation). The schoolyard bully resembles the character Joe Agate, introduced in the strip five years after the special was aired. Janice herself bears a slight resemblance to Lila.
- The idea for this special came from Sylvia Cook, a California nurse, who wrote a letter to Schulz asking if he could produce a short film in which the Peanuts characters explained the subject of cancer to children. Although Schulz initially expressed doubt, he eventually agreed to the idea, and decided to transform the originally proposed short film into a half-hour special.
- This special holds the distinction of being the first time that an animated series openly addressed the subject of cancer. As a result, it has been used at schools and hospitals to explain the serious subject to children.
- Snoopy the World Famous Surgeon makes a cameo appearance at the hospital.
- This special was nominated for the Emmy Award for Outstanding Animated Program (for Programming One Hour or Less). It was the last special to receive a nomination in that category, though subsequent specials (which were more documentary-style) would be nominated in the Outstanding Children's Program category.
- When Janice says "I bumped myself last week…", in closed captioning it says, "I found myself last week…".
- When Charlie Brown and Sally are talking about why Sally hates riding on the school bus, the sky changes colors out the window.
- It is extremely unlikely that Janice's hair could regrow as long as it does in such a short time frame. (The special takes place in a period of apparently five or six months, as it begins in the fall and ends by the start of spring.) It would take five to seven years for her hair to grow that long. This was most likely an intentional error.
- When Linus closes the door to his house, the door slam comes late.
- When Charlie Brown and Linus visit Janice in the hospital, she is at first in room 402. After Janice is given a shot and the boys come back to the room, her room number has changed to 404.
- Charlie Brown, Lucy, Linus and Sally are seen in the same classroom despite the fact that the first two are distinctly older than Linus, who in turn is older than Sally. Peppermint Patty is also seen in the classroom, while Marcie can be briefly seen in the school playground at the end of the special, despite it being shown that they go to a different school in the strip and other TV specials. This was allowed because Schulz did not consider material from the TV specials to be canon.
- When Charlie Brown and Linus are in school, Charlie Brown is sitting in front of Peppermint Patty. A few minutes later, Charlie Brown is sitting in front of Linus with Peppermint Patty behind both of them.
- Why, Charlie Brown, Why? on the Internet Movie Database.
- Why, Charlie Brown, Why? on the Big Cartoon Database.
- Why, Charlie Brown, Why? on AllMovie.
- Why Charlie Brown Why on TV Tropes.