He first earned respect in the art world with his Happenings. Pioneered with artists Claes Oldenburg and Allan Kaprow, in conjunction with musician John Cage, the "Happenings" were chaotic performance art that was a stark contrast with the more somber mood of the expressionists popular in the New York art world. The first of these was the 30-second The Smiling Worker performed in 1959.
In the early 1960s, he began attaching objects, particularly tools of autobiographical significance, to his canvases. Job #1 from 1962, in the collection of the Honolulu Museum of Art, which incorporates paint cans, paint brushes, a screwdriver, and a piece of wood is an example of such a pop art work. These provided commercial as well as critical success, but left Dine unsatisfied. In September 1966 police raided an exhibition of his work displayed at Robert Fraser's gallery in London, England. Twenty of his works were seized and Fraser was charged under the Obscene Publications Act of 1959, Dine's work was found to be indecent but not obscene and Fraser was fined 20 guineas. The following year Dine moved to London and continued to be represented by Fraser, spending the next four years developing his art.
According to James Rado, co-writer (with Gerome Ragni) of the rock musical Hair, it was a Dine piece entitled Hair which gave them the name.
The Virginia Museum of Fine Arts purchased six works by Dine, and in 1983 he was a juror in “The Next Juried Show” at the VMFA, judging prints and drawings. The juried shows at the VMFA were a series of biennial exhibitions covering all areas including Communication Arts, Craft Media, Painting & Sculpture, Photography, Video Arts, and Prints and Drawings, each on an every-other-year schedule. “The Next Juried Show” was the last of the series, however.
In 1984 the Walker Art Center in Minneapolis, Minnesota, exhibited his work as "Jim Dine: Five Themes". 1987 saw the publication of the book Jim Dine: Drawings 1973 - 1987, to coincide with a touring exhibition. In 1989 the Minneapolis Institute of Art hosted Jim Dine Drawings: 1973–1987. In 1983, he was elected into the National Academy of Design as an Associate member, and became a full Academician in 1994.
In 2004 the National Gallery of Art in Washington, D.C. organized the exhibition "Drawings of Jim Dine." In the summer of 2007 he participated in the Chicago public art exhibition "Cool Globes: Hot Ideas for a Cooler Planet." In Canada, he first exhibited at the Galerie de Bellefeuille alongside artists Chuck Close, Tom Hopkins and Jennifer Hornyak in 2009. Dine also exhibited regularly with the Alan Cristea Gallery in London and had a show there in April 2010.
As Conceptual art was emerging, Dine's use of iconic forms and repeated symbols attempted to understand how images create meaning. By singling out simple shapes and objects, and depicting them over and over, Dine suggests that they are important subjects for artistic study. Building on Marcel Duchamp's readymade sculptures, these ordinary objects take on a new, important, meaning solely because they were chosen by the artist and repeatedly studied. Isolating them and framing them in a gallery or museum space, Dine declares them worthy subjects to be celebrated in art, transforming them into something significant. Dine's work in this conceptual vein transforms Duchamp's skeptical gesture into part of a sincere investigation on how the artistic process elevates the ordinary.