During the 1960s, along with Andy Warhol, Jasper Johns, and James Rosenquist among others, he became a leading figure in the new art movement. His work defined the basic premise of pop art through parody. Favoring the comic strip as his main inspiration, Lichtenstein produced hard-edged, precise compositions that documented while it parodied often in a tongue-in-cheek manner. His work was heavily influenced by both popular advertising and the comic book style. He described pop art as "not 'American' painting but actually industrial painting." His paintings were exhibited at the Leo Castelli Gallery in New York City.

Whaam! and Drowning Girl are generally regarded as Lichtenstein's most famous works, with Oh, Jeff...I Love You, Too...But... arguably third.