Dine's first formal training took the form of night courses at the Art Academy of Cincinnati, in which he enrolled in 1952 at the age of 16,[1] while attending Walnut Hills High School.

[2] In 1954, while still attending evening courses, Dine was inspired by a copy of Paul J. Sachs' Modern Prints and Drawings (1954), particularly by the German Expressionist woodcuts it reproduced, including work by Ernst Ludwig Kirchner (1880–1938), Emil Nolde (1867–1956) and Max Beckmann (1884–1950)—"I was shocked by them" — and began creating woodcuts in the basement of his maternal grandparents, with whom he was then living.

Under printmaking teacher Donald Roberts (1923–2015) Dine experimented in lithography, etching, intaglio, dry paint and woodcuts.

[5] Dine's first exhibition was at the Reuben Gallery, where he also staged the elaborate performance Car Crash (1960),[5] which he describes as "a cacophony of sounds and words spoken by a great white Venus with animal grunts and howls by me.

"[6] Another important early work was The House (1960), an environment incorporating found objects and street debris, installed at the Judson Gallery.