Rovers have made the decision to wield the axe on a third manager this season following Sunday's 1-1 draw with local rivals Burnley and last week's FA Cup quarter-final defeat to Millwall.
A statement on the club's official website read: "Blackburn Rovers FC can confirm that Michael Appleton has been relieved of his duties as manager along with assistant manager Ashley Westwood, first team coach Darren Moore and head of senior recruitment Luke Dowling."
The club, without a win in eight games in all competitions, are 18th in the npower Championship table and just four points above the relegation zone.
Appleton left Blackpool to join Blackburn in the new year after just 65 days in charge at Bloomfield Road.
During 67 days in the Rovers job, Appleton won four, drew five and lost six of his 15 matches in charge.
In total, Appleton was the fifth man placed in charge of first-team affairs at Ewood Park this season.
Steve Kean's turbulent reign ended at the end of September, with Eric Black taking over on a temporary basis until former Rovers defender Henning Berg was appointed on November 1.
Berg last just 57 days before he was removed the day after Blackburn's 1-0 Boxing Day defeat at Middlesbrough.
Gary Bowyer was then placed in charge and he remained unbeaten during his four-game spell as interim manager, winning his first three matches against Barnsley, Nottingham Forest and Bristol City before drawing at Wolves.
Appleton continued the upturn in results following his appointment, losing just one of his first seven games and guiding Rovers to four victories, including a 1-0 win over Arsenal at the Emirates Stadium in the FA Cup.
That was the club's last win though, and Appleton leaves Blackburn on the back of five defeats in an eight-game winless run.
Rovers were knocked out of the FA Cup by Championship rivals Millwall last week and on Sunday needed an equalising goal from David Dunn deep into injury-time to rescue a 1-1 draw against Lancashire rivals Burnley.
Following the game at Ewood Park, Appleton said: "I hope it's damaging to Burnley and I hope it feels like it's the worst result they have ever had."