Waits, who has also starred in hit films, including 'Bram Stoker's Dracula' and Robert Altman's 'Short Cuts', was alerted to the ad by fans in Scandinavia where the spot is being shown in Sweden and Finland.
The Opel spot marks the fifth time the US singer has sued over his unique voice being used in ads without his permission.
In a statement Waits said: "Commercials are an unnatural use of my work. It's like having a cow's udder sewn to the side of my face. Painful and humiliating."
In 1993, Waits won £2m from US corn chip company Frito-Lay for mimicking his voice in radio ads.
A year later he sued his own record company for licensing 'Heartattack and Vine' for a Levi's commercial without consulting him.
In 2000 he was back in the courts, this time suing German carmaker Audi for using a song almost identical to his 'Innocent when You Dream', together with a gravelly impersonator's voice. A similar case occurred with a Lancia car advertisement in Italy.
Waits added: "I have a long-standing policy against my voice or music being used in commercials and I have lawyers over there investigating my options. But I got to tell you, it doesn't look good. This is the third car ad, after Audi in Spain and Lancia in Italy.
"If I stole an Opel, Lancia, or Audi, put my name on it and resold it, I'd go to jail. But over there they ask, you say no, and they hire impersonators. They profit from the association and I lose -- time, money, and credibility. What's that about?"
If you have an opinion on this or any other issue raised on Brand Republic, join the debate in the Forum.