Wesselmann was born in Cincinnati and attended university before serving in the Korean War during the early 1950s. While overseas he began to draw cartoons, and upon his return to the States he earned a psychology degree from the University of Cincinnati. He then enrolled at the Art Academy of Cincinnati and later the Cooper Union in New York City, finishing his studies by the late 1950s.
In the early 1960s, he began to make small collages and assemblages, which included everyday imagery from magazines, advertisements, and consumer culture. His work became more sexually charged in the late 1960s, culminating in the erotic series the Great American Nudes. Wesselmann’s work increased in scale in the 1970s, as he began painting simple objects on shaped canvases in his Standing Still Life series. Later in the 1970s, he created cut-out compositions in aluminum, enamel, and steel. In the last two years of his life, he returned to the female nude that had become so iconic in his work, producing the Sunset Nude series.
Wesselmann died in 2004 in New York, after heart surgery.