Warning: Spoilers follow
The novel is told through the eyes of an older, matured John Wheelwright who elaborates on the events surrounding his teenage friendship during the 1960s and 1970s with Owen Meany, whom John credits as being the reason he believes in God. Owen is impaired by an underdeveloped body: he is disproportionately short and needs to shout to be heard by because of his underdeveloped vocal chords (Owen's dialogue is written in all-caps for emphasis of this point). Owen's short stature makes him the butt of many jokes and cruel pranks but also the recipient of many special privileges, such as getting to play the baby Jesus Christ in a Christmas pageant because he's the only person who can fit in the crib.
The novel deals with several lofty spiritual issues, such as the importance of faith, social justice, and fate. John and Owen both offer criticisms of some aspects of organized religion and the hypocrisy of some religious people throughout the novel. The spiritual dimension is also emphasized by Owen consistently foretelling of his own impending death. Although he is always vague on specifics, such as when it will happen and how, he is quite certain that his death will be the result of his being an "instrument of God", that his death will serve some good purpose.
John is skeptical of Owen's unquestioned belief in the purpose of all things for several reasons, namely, his mother's premature death (as the result of the impact of a baseball hit by Owen), and his mother's failure to disclose his father's identity prior to her death. John is depicted as being spiritual apathetic throughout the novel until the conclusion, which 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.
The 1998 feature-length film Simon Birch, directed by Mark Steven Johnson, was loosely based on the novel. The film starred Ian Michael Smith, Joseph Mazzello, Ashley Judd, Oliver Platt and Jim Carrey. It omitted much of the latter half of the novel and altered the ending.