The novel is told through the eyes of a mature John Wheelwright, an English teacher at a private girls' school in Canada, who elaborates on the events surrounding his close friendship with Owen Meany during the 1950s and 1960s in a small town and at a private boarding school in New England. These, John makes clear, are responsible for his belief in God.
Owen is unusually short and his voicebox is fixed, so that he always sounds as if he is screaming. Owen's short stature makes him the butt of many jokes and pranks, though his peers do not generally dislike him. Children and adults alike seem drawn to and are almost protective of Owen. Owen is also the recipient of many special privileges, such as getting to play the baby Jesus in a Christmas pageant because he is the only actor who can fit in the crib and not cry.
The book begins with John giving an opening description of the (fictitious) town of Gravesend, New Hampshire, his old home, along with Owen and his mother, Tabitha. He and his mother live with John's grandmother, Harriet, and a wheelchair-bound (at the time of the beginning of the novel) maid, Lydia. John's paternity is a mystery, as his mother refuses to tell any of the family the man's name. Owen Meany becomes attached to Tabby, presumably because of his own home situation. His mother stares at things in her house, most notably the burned-out fireplace (John believes she was retarded), and his father is ill-equipped to deal. However, tragedy strikes when Owen hits a foul ball at a Little League game, which kills Tabitha. Her husband of a year, Dan, takes John under his wing and allows him to spend time at his house, an apartment at Gravesend Academy, where he teaches drama. The ball which killed her disappears, and John assumes Owen took it.
After Tabby's death, the whole community is affected, but life goes on. The narrator (John) introduces the characters of his three cousins: Hester, a tomboy, and Simon and Noah, both rough-housing older boys. Owen begs to be introduced, but embarrasses himself. All is forgiven, however, and although John is incestuously attracted to Hester, he puts these feelings away, chalking them to lust; especially after Owen admits he likes her.
Two major events that shape the narrative occur: The Gravesend Players, the local amateur acting group, put on a performance of A Christmas Carol while the boys' Episcopalian Church puts on a performance of The Nativity. Owen, with natural charisma, gets the parts of both baby Jesus and the Ghost of Christmas Yet to Come, but both performances become marred. In A Christmas Carol, during the last performance, Owen becomes overwhelmed and faints, nearly delirious with fever. He claims to have seen his own name on Scrooge's grave. Dan dismisses his concerns. In the Nativity performances, Owen sits up in his manger and shouts to his parents that it is a 'sacrilege' that they should attend, presumably something to do with a 'grave' injustice his parents were dealt at the hands of the Catholic Church, building a personal bigotry in Owen to them.
Soon, the two enter the prep school of Gravesend Academy, Owen with a scholarship and the financial backing of Harriet and John because his stepfather teaches there. John struggles, and Owen is there to help him. But these years are not simple. John finds no success with the search for his father, or the opposite sex, or his schoolwork, the last forcing him to see the bumbling school psychologist, Doctor Dolder. Owen takes up smoking and begins dating Hester while becoming 'The Voice', the pen name of his editorial in the school newspaper. This forces him into an antagonistic relationship with the new school headmaster, which ends with Owen being kicked out of school for printing false draft cards and the new headmaster being fired. All through school, Owen and John practice The Shot, a basketball move where John lifts Owen over his head so that he may dunk the basketball. They practice it intermittently over the following years, getting it to under three seconds (eventually).
Throughout the book, an older version of John, in Canada, has gone on massive tirades against the Reagan Administration. His teaching career is going moderately well, but he still struggles with his past life.
From here, the book changes. Owen becomes fixated upon his death, whose date he saw on the grave during the play: July 8, 1968. The Vietnam War begins, and Owen chooses to enter the Army as John begins work as graduate student to avoid the dreaded draft. Despite his determination to get into Vietnam, Owen ends up in Arizona as a casualty officer, bringing bodies of Arizona soldiers home from California. He later explains to John that he has had a recurring dream in which he saves many vietnamise children, but is killed in the process. He believes this to happen on the date he saw on the grave, and strives to fulfil his destiny. His actions create discord, but he stays the course.
John ends his graduate work and is about to be drafted. Owen, however, saws his finger off with a diamond wheel to avoid it. John later learns from Owen's diary that this was both to save his friend and to avoid John having to go to Vietnam, since Owen sees him in the dream and he will die there.
The story dives forward: John has become a teacher and has never lost his virginity, Dan is much older, Hester has become a punk rock superstar, and most everyone else is dead. Owen's funeral is held, and Mr. Meany confides in John that he allegedly never had sex with Owen's mother, and believes Owen to be 'like the Christ Child'. John is internally furious at the man, but says nothing, even when Mr. Meany says that he told Owen this 'fact' at the age of eleven, which John blames for Owen's belief he was a Son of God. John continues to dwell on his past, then finally tells the story of Owen's death:
As the date approaches, Owen invites John to visit him in Arizona for one last get-together. Owen has matured in his role, even praising Catholics, whom he had earlier despised. The duo, along with a Major, confront a low-class family whose son was killed in Vietnam. The entire bunch, save the boy's sister is openly angry with the military. As Owen and John and the major meet at the airport, Owen becomes ecstatic that he may not die today. However, a planeload of Vietnamese children arrive, and he knows it is time. He helps escort the kids into the bathroom of the airport, where the brother of the fallen soldier attempts to kill them all with a grenade. He throws it to John, who passes it to Owen on his command, then using The Shot to throw Owen to an upper window where the grenade explodes, maiming Owen but not the children. The attacker is killed by the major, who, along with John and some nuns, tries to save Owen. It is no use, however, and Owen dies. But the reasons for his voice and stature are made clear: He is able to easily communicate with the children, because he so much resembles them.
The novel deals with some serious spiritual issues, such as the importance of faith, matters of social justice, and the concept of fate, in the context of an outlandish narrative. Throughout the novel, John and Owen both offer criticisms of organized religion and religious hypocrisy. However, the spiritual dimension is repeatedly emphasized by Owen's foretelling of his own impending death. He is quite certain that he will die because he is an "instrument of God" and thus will serve some good and important purpose. He also believes that he knows the date of his death and that a heroic act on his part will kill him but also save some children. He is a bit unclear, however, about where and how this act will occur.
The narrative is constructed as the interweaving of three different stories of past John, present John, and Owen's life. There is the historical retelling of John's and Owen's childhood; the story of their (and particularly Owen's) adult lives; and the story of John's life after Owen's death. The three streams are brought together at the dénouement - the death of Owen. Owen had always predicted both the manner and the importance of his own death.
The familiar Irving setting (based on his own biography) of a New England private school relates the novel to the frameworks of his other works. However, other familiar Irving themes and settings (e.g. prostitutes, wrestling, and Vienna) are missing, or mentioned only briefly.
Young Johnny Wheelwright is skeptical of Owen Meany's unquestioned belief in the purpose of all things. He has certain reasons: namely, his mother's premature death (as the result of the impact of a baseball hit by Owen), and his mother's failure ever to disclose his father's identity. John is depicted as being spiritually apathetic as a youth, but the conclusion brings these spiritual pieces of the story together. Since the novel is written retrospectively, much of the novel takes the tone of John's newfound wisdom.
In the movie Milk Money, the elementary school is christened Owen Meany Elementary.
The movie Simon Birch (Jim Carrey and Ashley Judd), is based on the book.