[2] Pettibon came to prominence in the early 1980s in the southern California punk rock scene, creating posters and album art mainly for groups on SST Records, owned and operated by his older brother, Greg Ginn.

[8] Pettibon's artwork appeared on fliers, album covers and gift items (T-shirts, stickers and skateboards) for Black Flag through the early 1980s, and he became well known in the Los Angeles punk rock scene.

Pettibon works primarily with India ink on paper and many of his early drawings are black and white, although he sometimes introduces color through the use of pencil, watercolor, collage, gouache or acrylic paint.

He has stated that his interest in this technique is a result of the influence of artists such as William Blake and Goya, and the style of political editorial cartoons.

Yet his entire output, despite interludes of lyricism and nostalgia, and a running strain of stand-up humor, is a steady indictment of American culture as he has lived it over the past 60 years.

[18] In addition to his works on paper, Pettibon has also made animations from his drawings, live action shot-on-video films from his own scripts (each focusing on the American counterculture of the 1960s-1970s),[19] unique artist's books, fanzines, prints, and large permanent wall drawings that often include an arrangement of his own works on paper almost creating an installation of collage.

In the early 1990s, fellow artist Mike Kelley played guitar on an album of songs that Pettibon recorded for the independent label Blast First out of New York and London.

[21] Oliver Augst [de] 1208 Big Walnuts Yonder Black Flag Cerebral Ballzy Foo Fighters Mike Watt Minutemen Off!

Saccharine Trust Sonic Youth Unknown Instructors Pettibon began exhibiting his work in group shows in galleries in the 1980s.

In the late 90s, Pettibon to exhibited internationally including shows at the Tramway (arts centre) in Glasgow, Scotland, the Hammer Museum, Los Angeles and the 1997 Whitney Biennial.

In 2004, Pettibon participated in the Site Santa Fe Fifth International Biennial exhibition: Disparities and Deformations: Our Grotesque, curated by Robert Storr.

In 2008, Pettibon participated in the California Biennial, organized by Lauri Firstenberg, which featured one of his works as a large billboard on the Sunset Strip in Los Angeles.

Temporary exhibitions also show his paintings Broken at Last, and Sonic Youth cover signed by the artists and Kim Gordon.

In 2007, Pettibon participated in the Venice Biennial, Think with the Senses – Feel with the Mind: Art in the Present Tense, curated by Robert Storr for which he created a unique wall drawing installation.

As part of the honor, the Whitney Museum organized a solo exhibition that opened in the Fall of 2005, featuring new works and published an artist's book for the occasion.

In 2011, on the occasion of Ben Stiller and David Zwirner’s Artists For Haiti charity auction at Christie's, Pettibon's No Title (But the sand), sold for $820,000.