Wood was born in rural Iowa, 4 mi (6 km) east of Anamosa, in 1891, the son of Hattie DeEtte Weaver Wood and Francis Maryville Wood.[4][5] His mother moved the family to Cedar Rapids after his father died in 1901. Soon thereafter, Wood began as an apprentice in a local metal shop. After graduating from Washington High School, Wood enrolled in The Handicraft Guild, an art school run entirely by women in Minneapolis in 1910 (now a prominent artist collective in the city). He is said to have later returned to the Guild to paint American Gothic. A year later, Wood returned to Iowa, where he taught in a rural one-room schoolhouse.[6] In 1913, he enrolled at the School of the Art Institute of Chicago and performed some work as a silversmith.
From 1922 to 1928, Wood made four trips to Europe, where he studied many styles of painting, especially Impressionism and post-Impressionism. However, it was the work of the 15th-century Flemish artist Jan van Eyck that influenced him to take on the clarity of this technique and to incorporate it in his new works.