Nigel Spackman has been sacked after the board lost patience with Millwall's dismal start to the season.
Spackman had only been in charge since May, but, despite signing 19 players, his side had only won one of their 10 league matches.
That poor form forced chairman Stewart Till and his directors to act quickly to stop Millwall, who are already second from bottom of League One, sliding to a second consecutive relegation.
Spackman's assistant Willie Donachie will take over on a caretaker basis for Tuesday night's home match against Brentford.
Millwall will now look to appoint their sixth manager in 18 months, with Ray Wilkins, Steve Gritt, Dave Penney and Kevin Blackwell among the early contenders.
Till said: 'This has been a very difficult decision for both parties. We firmly believed that Nigel was the manager to take us back to the Championship.
'His qualities as a man and his vision for Millwall's future were impeccable, but unfortunately circumstances have dictated that things have not worked out as either he or we anticipated in the first ten games of the season.
'For a club of Millwall's size and ambitions clearly this has been a cause for concern, and consequently the Board have concluded, after discussion with Nigel, that we must seek a different approach.
'Our supporters will understand just how momentous a decision this has been for all of us to take so early in the season.
'But they will also recognise that the Board of Directors have to act in the best interests of the football club.'
Spackman has still to complete a full season as a manager after his previous two jobs at Sheffield United and Barnsley also ended prematurely.
He had been out of management for nearly five years when he arrived at The Den and his appointment was greeted with wide-spread surprise among Lions fans.
He was backed by the board in the transfer market but few of the players he brought in look up to the task of winning matches at this level.
With Millwall seven points from safety after Saturday's defeat against Northampton, their fifth successive loss, even Spackman admitted he was in trouble.
The decision to part company with him was inevitable and he said: 'Naturally I am very disappointed that results have not gone for us so far this season.
'I am still convinced that in time the squad of players at Millwall are capable of turning things around and moving up the table.
'In my short time at The Den, I very much enjoyed my association with Millwall and I wish the club all the very best for the future.
'As I stated on a number of occasions, this is a results based business, and time is not on the manager's side when results are not going your way.'