White men traveling to the jungle and discovering the dark side of human nature has been a common literary theme, from Joseph Conrad's Heart of Darkness to Paul Theroux's The Mosquito Coast. As a depiction of a dysfunctional family employing multiple narrators, The Poisonwood Bible has been compared to The Sound and the Fury by William Faulkner. As Kingsolver has mentioned Faulkner as an early literary influence, this comparison is particularly apt.

The subtitle of Book One—"The Things We Carried"—alludes to Tim O'Brien's award-winning short story "The Things They Carried." Like the American soldiers in Vietnam in O'Brien's story, the Prices carry both physical items and emotional baggage into the jungle, and they are weighed down by both.