The Scot has been under increasing pressure after failing to meet club owners Venkys' target of 16 points from their opening seven Championship matches, falling just two short.
Tim Sherwood had been linked with replacing the 44-year-old but Goal.com revealed earlier on Friday that Tottenham expect the former Rovers midfielder to turn down a return to Ewood Park, and remain part of the coaching staff under Andre Villas-Boas.
In a statement, Kean said: "For reasons that I cannot discuss on legal advice, it is with deep regret, given my hard work and service for the club for a number of years, that I have been forced to resign as manager of Blackburn Rovers Football Club with immediate effect, due to my position as team manager becoming untenable.
|2/1||Blackburn Rovers are 2/1 with bet365 to be promoted from the Championship this season|
"I wish to thank all the players and coaching staff for their great support and the majority of the fans, who now see their club heading towards an automatic promotion position back to the Premiership. I wish the club all the very best for the future."
Kean was promoted to the managerial role from first-team coach after Sam Allardyce's sacking in December 2010.
However, he oversaw the Lancashire club's relegation from the Premier League last season amid constant fan protests against his management and the Indian poultry firm's ownership of the club.
Kean claimed to have held "constructive" talks with Venkys earlier on Friday, after Blackburn's 2-1 defeat to Middlesbrough left them on 14 points after seven games.