Often cited as Fitzgerald's most clear attempt to write "science fiction," this story raises many questions about the writer and his cultural milieu. Because Fitzgerald's work is so closely associated with the Jazz Age and the Roaring Twenties, followed by the economic crash of 1929 and the lean years following, the story could be said to be a cautionary tale reflecting Fitzgerald's own immersion in a culture that valued youth and appearance over all. The notion of a person who could grow younger instead of older speaks directly to Fitzgerald's own personal apprehension about aging, but also possibly refers obliquely to his changing feelings about his wife Zelda.
As Benjamin Button's youthful energy and good looks overtake his old age, he becomes vain and judgmental. Benjamin's decision to leave his aging wife suggests he was embarrassed by appearing with her in public, since he looked youthful and vigorous beside her. Indeed, the story emphasizes Benjamin's growing disdain for his wife's appearance:
“There was only one thing that worried Benjamin Button; his wife had ceased to attract him. At that time Hildegarde was a woman of thirty-five, with a son, Roscoe, fourteen years old. In the early days of their marriage Benjamin had worshipped her. But, as the years passed, her honey-coloured hair became an unexciting brown, the blue enamel of her eyes assumed the aspect of cheap crockery--moreover, and most of all, she had become too settled in her ways, too placid, too content, too anaemic in her excitements, and too sober in her taste.”
The story also remarks upon the commonality of this state of mind by suggesting via the story’s narrator (an omniscient narrative point of view) that most people feel similarly to Hildegard as they grow older:
"She went out socially with him, but without enthusiasm, devoured already by that eternal inertia which comes to live with each of us one day and stays with us to the end."
Here again, the story implies a world weariness that Fitzgerald is often said to have expressed. Fitzgerald suffered from depression, and, coupled with his alcoholism and financial difficulties, it can be surmised that he must have often wished for a way to escape to the innocence of youth. The story can also be seen as a commentary upon the childlike qualities embraced during the 1920s, the self-indulgence and decadent behavior that left young adults ill-prepared for the sobering realities of the Great Depression.