Warhol was a leading figure in the visual art movement known as pop art. His works explore the relationship between artistic expression, advertising, and celebrity culture that flourished during the 1960s, and span a variety of media, including painting, silkscreening, photography, film, and sculpture.

Campbell's Soup Cans is a work of art consisting of thirty-two canvases, each painted with a Campbell's Soup can--one of each variety offered by the company at the time.

Sleep (1964) consists of looped footage of John Giorno, Warhol's lover at the time, sleeping for five hours and twenty minutes.

In third grade, Warhol had Sydenham's chorea (also known as St. Vitus' Dance), a nervous system disease that causes involuntary movements of the extremities, which is believed to be a complication of scarlet fever. Confined to bed, he drew, listened to the radio and collected pictures of movie stars. Warhol later described this period as very important in the development of his personality, skill-set and preferences.

Initially pursuing a career in commercial and advertising art, his first commission was to draw shoes for Glamour magazine. American photographer John Coplans later recalled that "nobody drew shoes the way Andy did. He somehow gave each shoe a temperament of its own, a sort of sly, Toulouse-Lautrec kind of sophistication, but the shape and the style came through accurately and the buckle was always in the right place."

The Factory became a well-known gathering place for distinguished intellectuals, drag queens, playwrights, Bohemian street people, Hollywood celebrities, and Warhol's wealthy patrons. Originally decorated with silver paint, fractured mirrors, and tin foil (adornments popular with amphetamine users during the 1960s) the Factory was famed for its groundbreaking parties.

In the program for a 1968 exhibition of his work, he wrote: "In the future, everyone will be world-famous for 15 minutes." This celebrated quote has become Andy Warhol's most well-known statement and led to the expression "15 minutes of fame" to convey the idea that celebrity will almost always be fleeting.

Warhol became the manager of The Velvet Underground in 1966, and they served as the house band at his art collective, also performing with his traveling multimedia show, The Exploding Plastic Inevitable. Their debut album, The Velvet Underground & Nico (with German singer and model Nico), was released in 1967 to critical indifference and poor sales but has since become critically acclaimed. In 2003, Rolling Stone called it the "most prophetic rock album ever made."

The Marilyn Diptych was created shortly after the actress died of a drug overdose on 5 August 1962. The images of Monroe are all based on a single publicity photograph from the film Niagara (1953). The use of two contrasting canvases illustrates the contrast between the public life of the star, who at the time was one of the most famous women on the planet, and her less glamorous private self, although this was not Warhol's original intention. The art collectors Burton and Emily Tremaine visited Warhol's home while he was working on the project and suggested that two canvases he had already made be presented as a diptych, to which Warhol responded, "gee whiz yes."

On June 3, 1968, radical feminist writer Valerie Solanas shot Warhol and art critic Mario Amaya at Warhol's studio. Before the shooting, Solanas had been a marginal figure in the Factory scene and appeared in the 1968 Warhol film I, a Man. Earlier on the day of the attack, Solanas had been turned away from the Factory after asking for the return of a script she had given to Warhol. Solanas was arrested the following day. By way of explanation, she said that Warhol "had too much control over my life." She was subsequently diagnosed with paranoid schizophrenia.