The move comes barely a month after drinks giant Diageo took control of Mallya's United Spirits, which owns Glasgow-based W&M, in a deal that transferred only 25% of the shares but a controlling stake in the voting rights.
Chief executive John Beard and director Ayani Nedungadi are also quitting with immediate effect, surprising whisky watchers.
With the Office of Fair Trading looking at the competition aspects of the UK part of the deal, it could yet be referred to the Competition Commission.
Analysts have indicated Diageo would not have a problem with selling W&M if necessary.
Mallya, a flamboyant character who has investments from airlines to Formula One, brought colour to a staid but highly successful industry when his group bought W&M in May 2007 for £700 million. His deal with Diageo, which is the largest Scotch producer, maintains his position as chairman of United Spirits. This means he may still have some sway over events at W&M, but analysts nonetheless saw his departure from the Glasgow board as his exit.