After earning a degree in Economic Geography from the University of California, Berkeley, de Grassi performed as a street musician in London before learning the carpentry trade from his cousin Will Ackerman who later founded the innovative instrumental record label Windham Hill. De Grassi's first album, Turning: Turning Back, was released by Windham Hill Records in 1978. De Grassi also recorded under RCA/Novus, EarthBeat!, and 33rd Street recordings. In addition, de Grassi started his own label, Tropo Records, which he now records under. He performs solo concerts worldwide, holds various guitar workshops and master classes throughout the year, and performs with the de Mania Trio, alongside bassist Michael Manring and percussionist Christopher Garcia. Fellow guitar players consider de Grassi to be among the most virtuosic living guitarists. Tom Wheeler wrote in Guitar Player magazine that his technique is "the kind that shoves fellow pickers to the cliff of decision: should I practice like a madman or chuck it altogether?"
De Grassi uses various guitars. Currently his primary touring/recording guitars are a custom Lowden F35c maple with a European spruce top and a custom Traugott R model Brazilian Rosewood with German spruce top. Other favorites are a custom Carlson sympitar (twelve sympathetic strings) maple with spruce top and a custom McCollum baritone (28" scale) paduk with Italian spruce top.