The 51-year-old Welshman was only appointed in May, but the club are 16th in the table after Saturday's 4-0 home defeat by Swindon Town.
Saunders lost 11 of his 20 league games in charge, and the Spireites are only four points above the relegation zone.
Chairman Dave Allen said: "We will not be rushed into making a decision on a new manager."
Chesterfield's last league victory was a 3-0 win over Southend on 20 October, and they have lost their last four games.
Saunders succeeded Paul Cook as Spireites manager, signing a two-year contract.
Cook had guided the Derbyshire side to the League One play-offs, where they lost to Preston, before leaving to take over at Portsmouth.
Former Wales international Saunders had previously managed Wrexham, Doncaster Rovers and Wolves, and ended last season in interim charge of Crawley Town, but was unable to stop them being relegated to League Two.
League One side Chesterfield have parted company with boss Dean Saunders after just six months in charge.