Dine is closely associated with the development of Pop art in the early 1960s. Frequently he affixed everyday objects, such as tools, rope, shoes, neckties, and other articles of clothing, and even a bathroom sink, to his canvases. Characteristically, these objects were Dine’s personal possessions. This autobiographical content was evident in Dine’s early Crash series of 1959–60 and appeared as well in subsequent recurrent themes and images, such as the Palettes, Hearts, and bathrobe Self-Portraits. Dine has also made a number of three-dimensional works and environments, and is well-known for his drawings and prints. He has written and illustrated several books of poetry.

In 1965, Dine was a guest lecturer at Yale University, New Haven, and artist-in-residence at Oberlin College, Oberlin, Ohio. He was a visiting artist at Cornell University, Ithaca, New York, in 1967. From 1967 to 1971, he and his family lived in London. Dine has been given solo shows in museums in Europe and the United States. In 1970, the Whitney Museum of American Art, New York, organized a major retrospective of his work, and in 1978 the Museum of Modern Art, New York, presented a retrospective of his etchings. Dine lives in New York and Putney, Vermont.