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Love's Greatest Mistake was based on the serialized Liberty Magazine story of the same name. It all begins when Honey McNeill (Josephine Dunn) leaves her home town of Bangor, Maine to visit her married sister Jane (Evelyn Brent) in New York. En route, Honey meets and falls in love with banker William Ogden (Frank Morgan). She confides in Ogden that she expects her visit to Jane to be a dull one, because nothing earth-shattering ever happens in her sister's household. Little does she realize that Jane is presently engaged in an extramarital affair with oily Don Kendall (William Powell). Our hapless heroine gets mixed up in a blackmailing plot hatched by Don, from which she is rescued by Ogde -- who nonetheless steps gallantly aside when a younger, handsomer man (James Hall) comes into Honey's life.