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Grant Wood was born in 1891 near Anamosa, a small town in eastern Iowa. When he was ten years old, following the death of his father, Wood moved with his mother and sister to Cedar Rapids. During his teens, Wood was a metalworking apprentice and graduated from Washington High School. The family moved to Minneapolis thereafter and Wood studied art at The Handicraft Guild. Eventually, Wood relocated to Chicago, where he matriculated at the School of the Art Institute of Chicago in 1913, briefly joined the Kalo Shop to work as a silversmith, and then co-founded the Volund Crafts Shop with Kristoffer Haga. While at Kalo, Wood lived in the barn and was notorious for showering in the summertime by running naked through rainstorms. In 1916, he re-enrolled at the Art Institute but dropped out after eleven days as he was unable to secure any work at all to pay for food or cover living expenses. When an old friend from Cedar Rapids offered Wood some money, he returned to Iowa for good. At the time, his mother was in ill health, so Wood supported her and his sister, who had both previously moved back from Minneapolis, by teaching grammar school. In his spare time, Wood continued to pursue his art, producing early paintings in an Impressionistic style as well as ink and charcoal drawings, lithography, ceramics, and other types of media.

In the mid-1920s, Wood made multiple trips to Europe. Initially, he immersed himself in Impressionism and Post-Impressionism, seeking to enhance his existing manner of painting. However, in 1928, Wood embarked on a pivotal journey to Munich to supervise the production of stained glass that he designed for the Veterans Memorial Building in Cedar Rapids. On this visit, Wood experienced a breakthrough while studying the work of the Northern Renaissance, in particular, paintings by German and Flemish masters of the 15th century, such as Hans Memling and Jan van Eyck. Their work inspired Wood to move suddenly away from Impressionism and toward a solid, clear realism to render more powerfully the rural people and places that he felt were underrepresented in the art of his day. In 1929, Wood produced Woman with Plants, which is a portrait of his mother in the Flemish style with a rolling landscape in the background. This painting went largely unnoticed, but everything changed for Wood in 1930 when he painted American Gothic. The now iconic work shows an older farmer with a pitchfork looking forward stoically and a younger woman beside him looking disapprovingly at something off to the side. Behind them is a Gothic Revival-style cottage whose central windows fill the space between the pair. Immediately upon its completion, American Gothic won a $300 prize and was exhibited at the Art Institute of Chicago, where it remains a part of the permanent collection to this day.

American Gothic caused a sensation for both its starkness and ambiguity. On the one hand, the subjects are incredibly lifelike and so foregrounded that they appear on the verge of coming through the picture plane. On the other hand, there has long been some confusion as to the relationship between the depicted pair. In reality, Wood's sister was the model for the younger woman and his dentist stood in for the older farmer. However, people regularly disagree on whether the woman is the farmer's wife or daughter. Likewise, there is wide variance in how people interpret the painting. Is American Gothic a celebration of Midwestern simplicity and determination, a parody of the stultifying conformity of rural life, or a clever combination of both? Wood himself was somewhat inconsistent on the subject, although he did generally describe the painting as a tribute to its subjects and setting. With American Gothic, Wood grew relatively famous overnight and became much in demand. He produced memorable landscapes, including Stone City (1930) and The Midnight Ride of Paul Revere (1931), which further elevated his reputation. In 1932, Wood used his professional clout to found the Stone City Art Colony near Cedar Rapids and lent support to other artists during the Great Depression. In 1934, Wood joined the University of Iowa as a member of its art faculty. He was also named director of the Public Works of Art Project in Iowa that year.

Given the evolution of Wood's aesthetic philosophy and his newfound influence, he positioned himself as a major proponent of American Regionalism. Having turned away from Europe as a contemporary influence and seeking to distance himself from America's urban culture centers, Wood published his famous essay, "Revolt Against the City," in 1935. Drawing on the ideas of the writers Jay Sigmund and Ruth Suckow, Wood endeavored to articulate how and why Americans should create art grounded in where they are and what they know. While Wood was known to exaggerate his role as an authentic Midwesterner by donning bib overalls and claiming that milking cows led to his best ideas—despite having left farm life behind in his youth—he nonetheless was quite serious about the aims of Regionalism and became its de facto spokesman. As the Depression lingered, cities became sites of mass unemployment and fewer artists could travel to Europe. These factors in turn made Regionalism seem like a necessary reframing of American artistic theory and practice.

After being single most of his life, Wood quickly married a woman named Sara Maxon in 1935. His friends worried about their abrupt union, largely because Wood was a closeted homosexual. Wood and Maxon endured a challenging relationship and they divorced in 1939. Simultaneously, Wood ran afoul of the IRS for tax evasion. In 1940, Wood opted to take a leave of absence from the University of Iowa since he felt the faculty no longer supported Regionalism given the rise of abstract movements in American art. Before long, Wood developed pancreatic cancer and died a day before turning fifty-one at the university hospital in 1942. Wood is buried where he was born, in Anamosa, Iowa. Upon Wood's death, his sister was fittingly bequeathed his entire estate. When she died in 1990, Wood's personal belongings and assorted works were donated to the Figge Art Museum in Davenport, Iowa. Wood is obviously most remembered for American Gothic, but he left behind quite an impressive array of portaits, landscapes, and still lifes. Moreover, he produced compositions in a wide range of forms besides painting and helped put Regionalism literally and figuratively on the map. Today Wood's artwork is held by the Art Institute of Chicago, the Metropolitan Museum of Art in New York City, the Smithsonian American Art Museum in Washington, DC, the Cedar Rapids Museum of Art, the Figge Art Museum in Davenport, and many other notable institutions.