Saunders, who took over from Paul Cook in May, leaves the Spireites 15th in Sky Bet League One, with the reverse to Swindon a fourth in a row.
His assistant Brian Carey has also left the club.
A club statement read: "Chesterfield have parted company with manager Dean Saunders and his assistant Brian Carey following a 4-0 defeat at home to Swindon Town.
"An interim management team, which will be announced in due course, will take temporary charge prior to the appointment of a new manager."
Chairman Dave Allen added: "We will not be rushed into making a decision on a new manager."
Saunders, who made five changes to his side for the clash with the Robins, was not expecting the sack when he addressed the media after the game, but knew he had to start getting results.
He said: "It's a results business and I have to get enough results for us to regroup as a club.
"As a manager all you try and do is survive long enough to get it right
We're not in a crisis, we've just hit a bad patch and a couple of good results get us back to where we should be."
Source : PA