Waits has a distinctive voice, described by the MusicHound Rock Album Guide as sounding "like it was soaked in a vat of bourbon, left hanging in the smokehouse for a few months and then taken outside and run over with a car." (Waits's voice was also described in one court decision as follows: "Waits has a raspy, gravelly singing voice, described by one fan as 'like how you'd sound if you drank a quart of bourbon, smoked a pack of cigarettes and swallowed a pack of razor blades... Late at night. After not sleeping for three days.'" Waits v. Frito-Lay, Inc., 978 F.2d 1093 (1992 9th Cir.)) With this trademark growl, as well as his experimental tendencies and a love of pre-rock Americana styles such as blues, jazz, and Vaudeville, Waits has built up a distinctive musical persona.

Lyrically, Waits's songs are known for atmospheric portrayals of bizarre, seedy characters and places, although he has also shown a penchant for more conventional and touching ballads. He has a cult following and has influenced subsequent songwriters, despite having little radio or music video support. His songs are best known to the general public in the form of cover versions by more visible artists, such as Eagles, The Ramones, Bruce Springsteen, and Rod Stewart. Although Waits's albums have met with mixed commercial success in his native United States, they have occasionally achieved gold album sales status in other countries.