Before Devo, Gerald played bass, after switching from drums, with Kent, Ohio blues band 15-60-75, also known as "The Numbers Band." Casale caused friction in the group by suggesting they incorporate advertising jingles and other "lowbrow culture" elements into their music. He was forced out of the band, allegedly, after slipping either an ape mask, or a Colonel Sanders mask on during a performance. Casale began to focus primarily on Devo at this point, developing the band's distinct visual style, and working closely with Mothersbaugh and Lewis to create a performance art group.
Describing himself as Devo's "chief strategist", Casale is responsible for much of Devo's distinct visual appearance, designing their costumes including the Energy Dome. He also directed most of Devo's music videos, along with Chuck Statler. Casale also directs music videos for other artists, including Rush, The Cars, Soundgarden, Silverchair, and Foo Fighters. In addition to music video, Casale also directed a number of television commercials, including ads for Diet Coke and Honda Scooters featuring Devo, as well as for Coco's restaurants, and Miller Lite. Distinctive elements of Casale's visual style include dutch angles, desaturated color, and color washes on images.
In 2005, Casale created a solo project, Jihad Jerry & the Evildoers. The album, Mine is Not a Holy War was a more blues-oriented album than Devo's output and featured performances of two early Devo songs, along with a B-side from 1982, and a cover of "He's Always There" by The Yardbirds. While Jihad Jerry never toured, the theatrical character appeared with Devo at several shows in 2006, as well as on the Fox News program "Red Eye." Casale abandoned the Jihad Jerry character in 2007; however, he donned the Jihad Jerry turban for a performance with UK-based DJ and producer Adam Freeland at the South by Southwest music festival in 2009. In 2009 he participated in the project Die Alten Maschinen, together with the Czech producer and composer Moimir Papalescu. EP "To Be Or Not", in which Gerald Casale participated as an author, was released on vinyl. At the same time, the song "To Be Or Not" in a different version appeared on the album "Songs About Love And Machines", which was released in 2010.
Casale has played several types of bass guitars, left-handed, mostly heavily customized. Among the most distinctive is a teardrop shaped bass, actually a Gibson Ripper with its horns sawed off and a thick arm padding added to the top side, as seen in videos for "Satisfaction" and "Come Back Jonee". From 1981 on, in performance, Gerald Casale has used a right-handed Steinberger L-Series bass guitar, played upside down. He has also played various keyboard basses, including a MiniMoog, a custom six-oscillator Moog keybass, and a Roland D-50. Currently, Casale uses a Korg synthesizer for bass.