The club confirmed that assistant Mark Venus would take over from the 49-year-old, who has been at the helm since 2010, until a permanent successor is appointed.
"Assistant manager Mark Venus will take charge of the team until further notice."
Boro have won just two of their first 12 league games this season and currently sit 16th in the Championship. They went down 3-2 at struggling Barnsley on Saturday.
The statement continued: "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.''
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