The 51-year-old joined the club in 2007 and was the sixth-longest serving manager in the top four divisions in England behind Sir Alex Ferguson, Arsene Wenger, David Moyes, Tony Pulis and Exeter's Paul Tisdale.
Jackett led the Lions to the FA Cup semi-final this season but a run of four defeats in the last five games saw the club finish just two points above the npower Championship drop zone.
In a statement on the club's official website, he said: "After almost six seasons I personally feel the time is right for a new challenge, and also for a new manager to come into Millwall with fresh ideas, to take the club forward towards its long term goal of reaching the Premier League.
"I would like to thank the chairman, the board of directors, players, members of staff and supporters of Millwall for their considerable backing. I have thoroughly enjoyed my time at Millwall. My family and I will always have a strong link and affinity with the club."
Chairman John Berylson was keen to keep Jackett at the club, but respected his decision to move on.
He added: "On behalf of the board of Millwall Football Club, I want to express my thanks to Kenny for his fantastic service and achievements over the past five-and-a-half years.
"He has played a major role in creating a stable environment at Millwall which hadn't been the case prior to his arrival.
"On a personal level, whilst respecting Kenny's decision, I wish I could have persuaded him to change his mind. He was my first acquisition as chairman of the club and has proved himself to be one of the best.
"I am losing a great manager, but he will remain a good friend and hopefully, golf partner. I know everyone associated with Millwall, management, staff, players and fans, will wish Kenny all the very best with his future endeavours, except for those times when he might oppose us on the pitch."
Source: PA
Source: PA