The North-East outfit have won just five Championship games in 2013 and are currently 16th in the table after losing 3-2 at home to struggling Barnsley at the weekend.
It continues a terrible run of form for Boro who were top of the Championship table in November 2012 and still in the top three at the turn of the year.
Boro were also eliminated from the League Cup by League Two struggles Accrington this season and attendances have also plummeted at the Riverside
A statement from the club read: "Middlesbrough Football Club have today announced that manager Tony Mowbray has left the club with immediate effect.
"Assistant manager Mark Venus will take charge of the team until further notice.
"The club would like to place on record their sincere thanks to Tony Mowbray for all of his substantial efforts, dedication and integrity.
"He leaves with the very best wishes of all at the club."