His masterpiece "American Gothic," featuring a stern farmhouse and two figures, became one of America's most recognizable artworks, though often misinterpreted as earnest rather than satirical. Wood's regionalist approach rejected European modernism and urban American art world conventions, celebrating provincial America through meticulous realism and wry humor.

Works like "Daughters of Revolution" and "Daughters of the American Revolution" demonstrate his satirical edge, critiquing American society while chronicling rural traditions. Wood's careful draftsmanship and symbolic compositions influenced American regionalist movement, establishing Iowa as artistic center through his teaching and community advocacy.

His early death from cancer cut short a remarkable artistic career at age fifty-one. Wood's legacy encompasses visual art, regional identity, and complex meditations on American character combining affection with critique. Today, his paintings command substantial prices and his work remains central to American art history conversations about regionalism, modernism, and artistic identity.