Appleton only replaced former boss Henning Berg on January 12 having been recruited from fellow Championship side Blackpool - where he had previously been manager for just 65 days - but has been dismissed following a disappointing run of results that have brought just four wins from 15 games.
The 37-year-old - who began the season in charge of Portsmouth - becomes the fourth manager to be sacked by controversial owners Venky's since taking over the club in November 2010.
Appleton's brief tenure included a famous FA Cup fifth round win at Arsenal but his side were then knocked out in a quarter-final replay by Millwall earlier this month and have sunk to 18th in the Championship table.
A brief statement on the club 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 Sports PR Company, which represents Appleton, later released a statement
from him via Twitter which read: "I am disappointed to be leaving Blackburn Rovers. I would like to thank the players and wish them all the best for the rest of the season. I would also like to say thanks to the fans who have made me feel so welcome over the past few months."
It has been reported that reserve team boss Gary Bowyer, who took temporary charge of the side following Berg's departure, will resume his caretaker role until the end of the season.
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 lasted just 57 days before he was removed the day after Blackburn's 1-0 Boxing Day defeat at Middlesbrough.
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."
Rovers' bosses over Venky's ownership
Venky's buy-out was completed on November 19, 2010 and less than a month later Allardyce, who had been in charge at Ewood Park for just under two years, was sacked.
On December 21, Allardyce claimed a third party must have been at work in engineering his dismissal, as he told Sky Sports News: "Having never really met the new owners and had little dialogue, somebody somewhere has obviously said something derogatory to get me out of this job."
Record: P90 W32 D24 L34 - win percentage 36%.
The Scot, who initially served as caretaker boss following Allardyce's dismissal, was given the job on a permanent basis in January 2011 on a contract until June 2013.
Kean, who was in charge as Blackburn suffered relegation to the npower Championship at the end of the 2011-12 season, was deeply unpopular with Rovers fans and resigned in September last year after describing his position as "untenable" in the face of supporter boycotts of the stadium.
Record: P74 W21 D16 L37 - win percentage 28%.
The Norwegian lasted just 10 matches and 57 days at the club, having been appointed in November 2012 as Kean's permanent successor. He had said in May 2012 that "no manager with real credibility" would take on the job.
Record: P10 W1 D3 L6 - win percentage 10%.
Blackburn was Appleton's third job of the season when he was appointed on January 12, having previously been in charge at Portsmouth and Blackpool, whom he left to take charge at Ewood Park. His sacking was confirmed today with the club 18th in the Championship and after 15 games at the helm.
Record: P15 W4 D5 L6 - win percentage 27%.