While at Chouinard, Ruscha edited and produced the journal Orb (1959–60) together with Joe Goode, Emerson Woelffer, Stephan von Huene, Jerry McMillan, and others.

Ruscha achieved recognition for paintings incorporating words and phrases and for his many photographic books, all influenced by the deadpan irreverence of the Pop Art movement.

His work is also strongly influenced by the Hollywood film industry: the mountain in his Mountain Series is a play on the Paramount Pictures logo;[10] Large Trademark with Eight Spotlights (1962) depicts the 20th Century Fox logo,[11] while the dimensions of this work are reminiscent of a movie screen; in his painting The End (1991) these two words, which comprised the final shot in all black-and-white films, are surrounded by scratches and streaks reminiscent of damaged celluloid.

Among his first paintings (SU (1958–1960), Sweetwater (1959)) this is the most widely known, and exemplifies Ruscha's interests in popular culture, word depictions, and commercial graphics that would continue to inform his work throughout his career.

[15] More recently, his "Metro Plots" series chart the various routes that transverse the city of Los Angeles by rendering schematized street maps and blow-ups of its neighborhood sections, such as in Alvarado to Doheny (1998).

[21] Since 1964, Ruscha has been experimenting regularly with painting and drawing words and phrases, often oddly comic and satirical sayings alluding to popular culture and life in LA.

[23] In the 1970s, Ruscha, with Barbara Kruger and Jenny Holzer, among others, began using entire phrases in their works, thereby making it a distinctive characteristic of the post-Pop Art generation.

[30] From 1980, Ruscha started using an all-caps typeface of his own invention named "Boy Scout Utility Modern" in which curved letter forms are squared-off (as in the Hollywood Sign)[31] This simple font is radically different from the style he used in works such as Honk (1962).

In his drawings, prints, and paintings throughout the 1970s, Ruscha experimented with a range of materials including gunpowder, vinyl, blood, red wine, fruit and vegetable juices, axle grease, chocolate syrup, tomato paste, bolognese sauce, cherry pie, coffee, caviar, daffodils, tulips, raw eggs and grass stains.

In the portfolio of screenprints News, Mews, Pews, Brews, Stews, Dues (1970), produced at Editions Alecto, London, rhyming words appear in Gothic typeface, printed in edible substances such as pie fillings, bolognese sauce, caviar, and chocolate syrup.

[39] Notably different from many of Ruscha's works of the same period, most obviously in its exclusion of text, his series of Miracle pastel drawings from in the mid-1970s show bright beams of light burst forth from skies with dark clouds.

[40] In the 1980s, a more subtle motif began to appear, again in a series of drawings, some incorporating dried vegetable pigments: a mysterious patch of light cast by an unseen window that serves as background for phrases such as WONDER SICKNESS (1984) and 99% DEVIL, 1% ANGEL (1983).

Created as part of a public-art commission, The Back of Hollywood (1976–77) was made from a large sheet of sateen on a billboard and situated opposite the Los Angeles County Museum of Art, designed to be read in the rear-view mirror of a moving car.

[42] In 1989, Ruscha decorated a pool for his brother Paul at his house in Studio City, Los Angeles, with a supersized luggage label: on a black tiled background are the words Name, Address and Phone, complete with dotted lines.

[43] In 1998, Ruscha was commissioned to produce a nearly thirty-foot high vertical painting entitled PICTURE WITHOUT WORDS, for the lobby of the Harold M. Williams Auditorium of the Getty Center.

[45] For his first public commission in New York in 2014, Ruscha created the hand-painted mural Honey, I Twisted Through More Damn Traffic Today for a temporary installation at the High Line.

[52] In 2022, he teamed up with (RED) and Gagosian Gallery to create a limited-edition silk twill scarf—featuring his drawing Science Is Truth Found (1986)—to help provide more equitable access to COVID-19 relief.

[57] Photography has played a crucial role throughout Ruscha's career, beginning with images he made during a trip to Europe with his mother and brother in 1961, and most memorably as the imagery for more than a dozen books that present precisely what their titles describe.

[63] With the assistance of a Guggenheim Fellowship, Ruscha arranged in Premium a scenario which he first projected in his photo-book Crackers from 1969 and subsequently transformed into a film which features Larry Bell, Leon Bing, Rudi Gernreich, and Tommy Smothers.

Miracle contains the essence of the artist's same-named painting, inasmuch as the story is told of a strange day in the life of an auto mechanic, who is magically transformed as he rebuilds the carburetor on a 1965 Ford Mustang.

[65] Artist Tom Sachs' 2018 short film Paradox Bullets stars Ruscha in the role of a hiker lost in the desert and guided only by the voice of Werner Herzog.

[67] Interviews with Ruscha are included in the documentaries Dennis Hopper: The Decisive Moments (2002), Sketches of Frank Gehry (2005), The Cool School (2008), Iconoclasts (2008), and How to Make a Book with Steidl (2010), among others.

[68] In 1962 Ruscha's work was included, along with Roy Lichtenstein, Andy Warhol, Robert Dowd, Phillip Hefferton, Joe Goode, Jim Dine, and Wayne Thiebaud, in the historically important and ground-breaking New Painting of Common Objects, curated by Walter Hopps at the Pasadena Art Museum.

[70] For the Venice Biennale in 1976, Ruscha created an installation entitled Vanishing Cream, consisting of letters written in Vaseline petroleum jelly on a black wall.

While driving in a 1950 Ford sedan, the 18 year old artist drew inspiration from dilapidated gas stations, billboards, and telephone poles cross the great expanse of the land.

From September 2023 to January 2024, the Museum of Modern Art in New York City exhibited the retrospective ED RUSCHA / NOW THEN featuring over 200 works across mediums, including The Chocolate Room.

[79][80] In 2003, Ed Ruscha curated Emerson Woelffer: A Solo Flight, a survey of the work of the late Los Angeles-based Abstract Expressionist, for the inaugural exhibition of the Gallery at REDCAT (Roy and Edna Disney/CalArts Theater).

[115] In 2010, during British prime minister David Cameron's first visit to Washington, President Barack Obama presented him with a signed two-color lithograph by Ruscha, Column With Speed Lines (2003), chosen for its red, white and blue colors.

[123][124] Burning Standard (1968) from the collection of Alan and Dorothy Press, which sold for $22.2 million with fees at Christie's New York in 2023, is the most valuable of Ruscha gas station paintings to sell at auction to date.

The "Streets of Los Angeles" archive acquired by the Getty Research Institute begins with the photographic and production material for Ruscha's landmark 1966 book Every Building on the Sunset Strip, and includes the original camera-ready three-panel maquette used for the publication.