After being a guest performer on his dad's Them Or Us album in 1984, he would sign to 'Chrysalis' to release his debut solo shot, Havin' A Bad Day (1987). Since his debut was basically ignored he recruited a band proper in the form of himself on guitar with Scott Thunes (bass), drummers Steve Smith (of Journey), Bobby Blotzer (of Ratt), Terry Bozzio (of Jeff Beck Band), and Fiona (of Flannigan; vocals) to release a MTV savvy version of his father's My guitar Wants To Kill Your Mamma (1988) and used it as the title track to his 1993 album of the same name. Three more albums have thus far followed with a basic hard rock Van Halen mimicry for Confessions (1991), Shampoohorn (Z) (1993) featuring his brother, and Automatic (2001), an album that saw him take more of a back seat since the death of his father. Go with What You Know (2006) and Via Zammata (2015) would follow.
In the mid-1990s, Zappa voiced the character Ajax Duckman on the animated series Duckman. He also briefly appeared in the television sitcom Normal Life with sister Moon Unit Zappa and former Laverne & Shirley star Cindy Williams. He composed and performed the theme music for The Ben Stiller Show (the solo from Spinal Tap's Break Like the Wind).
In "Weird Al" Yankovic's 2003 album Poodle Hat, Zappa performs the opening guitar solo and lends his vocal talents to the track, Genius in France. In 2006, Zappa organized the Zappa Plays Zappa tour by assembling a band of young musicians with a view to bring the music of Frank Zappa to a younger audience.
In 2016, Zappa went on tour to celebrate the 50th anniversary of the release of Frank Zappa's album Freak Out!