Born in Norman, Oklahoma, David Salle pursued his formal art education at the California Institute of the Arts, where he studied under the conceptual artist John Baldessari. He emerged as a significant voice in the New York art scene during the early 1980s, gaining recognition for his distinctive approach to postmodern painting.

His signature style involves the layering of fragmented, often contradictory images across a single canvas, utilizing a diverse range of media including oil paint, photography, and printmaking. His work frequently explores the tension between representation and abstraction, drawing on a vast visual vocabulary that spans classical art, film stills, and commercial design.

Salle continues to be a fixture in the contemporary art world, maintaining a studio practice in East Hampton, New York. His work remains a subject of ongoing critical discourse regarding the evolution of painting in the late 20th and early 21st centuries.