The 37-year-old joined from Blackpool after a similarly short-lived spell at Bloomfield Road.
Appleton only replaced Hennig Berg in the Ewood Park hotseat on January 12 but has been dismissed following a poor run of results.
Despite knocking Arsenal out of the FA Cup earlier this season, Rovers have only won four of their past 15 games.
Following Sunday's 1-1 draw with bitter rivals Burnley, Blackburn are 17th in the Championship table, four points clear of the drop zone in their first season since relegation from the Premier League.
An eight-game winless streak was enough to ensure another change of management for the Championship side.
Blackburn Rovers have had an extremely turbulent season so far, and a run of results which saw them claim just three points from seven Championship games means the club are now looking for their fourth permanent manager of the season.
Steve Kean was given his marching orders after a handful of Championship games following the club's relegation from the Premier League.
Berg lasted just 57 days in charge of the Lancashire club, the shortest spell of any permanent manager in their history.