The woman is dressed in a colonial print apron evoking 20th-century rural Americana while the man is adorned in overalls covered by a suit jacket and carries a pitchfork.

[10] After obtaining permission from the house's owners, Selma Jones-Johnston and her family, Wood made a sketch the next day in oil paint on paperboard from the front yard.

This sketch depicted a steeper roof and a longer window with a more pronounced ogive than on the actual house – features which eventually adorned the final work.

One judge deemed it a "comic valentine", but a museum patron persuaded the jury to award the painting the bronze medal and a $300 cash prize.

It was thus seen as part of the trend toward increasingly critical depictions of rural America along the lines of, in literature, Sherwood Anderson's 1919 novel Winesburg, Ohio, Sinclair Lewis's 1920 Main Street, and Carl Van Vechten's 1924 The Tattooed Countess.

Wood assisted this interpretive transition by renouncing his bohemian youth in Paris and grouping himself with populist Midwestern painters such as John Steuart Curry and Thomas Hart Benton, who revolted against the dominance of East Coast art circles.

"[1] Wood intended the painting to depict the farmer and his daughter as survivors, to pay homage to the strength of the rural community, and to provide reassurance in a time of great economic upset.

[25] Davenport took the inspiration back even further, while seeing similarities to Northern Renaissance paintings of married couples, according to Davenport, American Gothic recalls, "the Egyptian prince Rahotep, holding the flail of Osiris, beside his wife Nufrit—strict with pious rectitude, poised in absolute dignity, mediators between heaven and earth, givers of grain, obedient to the gods.

"[26] The Depression-era understanding of the painting as depicting an authentically American scene prompted the first well-known parody, a 1942 photo by Gordon Parks taken in Washington, D.C. of cleaning woman Ella Watson.

It has also been parodied in marketing campaigns, pornography, and by couples who recreate the image photographically by facing a camera in the same way, one of them holding a pitchfork or other object in its place.

[29] A parody of the painting by illustrator Chris Riddell appeared in The Observer on 19 January 2025 depicting Elon Musk as the father and Donald Trump as the daughter wearing a MAGA broach, a distressed Statue of Liberty can be seen through the Gothic window.