After a two-year hitch in the Marine Corps, during which he reached the rank of corporal, DeGeneres hosted a radio program called New Wave New Orleans in the late 1970s, broadcast on WRNO-FM. He played bass guitar in The Cold, a new-wave band based in New Orleans in the early 1980s.
He originated the role of "Mr. Hands" in Walter Williams' Mr. Bill short films in the mid-1970s. According to the 1986 book Saturday Night: A Backstage History of Saturday Night Live, DeGeneres sued Williams in federal court in 1979, asking for his name on the Mr. Bill copyright and for half of all profits the Mr. Bill character produced. After a two-day hearing, DeGeneres received an undisclosed portion of merchandising rights to Mr. Bill. However, the judge ruled that Mr. Bill was Williams' "basic idea and concept."
In the mid-1980s, DeGeneres co-founded the short-lived rock band called House of Schock with The Go-Go's drummer Gina Schock. In 1998, he played keyboards for the New Orleans-based band Cowboy Mouth. In March 2006, he appeared on The Ellen DeGeneres Show with Cowboy Mouth to perform their song "The Avenue." In December 2006, he became the permanent rhythm guitarist in Cowboy Mouth, but left in September 2007 to pursue additional TV projects. He does play guitar on their 2007 Live DVD The Name of the Band is Cowboy Mouth.
Vance DeGeneres was a correspondent on The Daily Show from 1999 to 2001. DeGeneres would occasionally present a feature done in the style of a Dateline NBC report, known as "Tale of Survival." In it, a trivial incident was reported as if it had been dangerous and serious, such as the time a cat was stuck in a tree for over a week. Between pre-filmed portions, DeGeneres would appear in the studio hiding behind various set decorations or apparatus, describing the events in greater frightful detail. Unlike other Daily Show pieces, this one would be divided by a commercial break to accentuate the anticlimactic aspect.