The 49-year-old loses his job following Saturday's 3-2 defeat at lowly Barnsley.
In a statement this evening, the club said: "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."
Mowbray's assistant Mark Venus will take temporary charge of proceedings at the Riverside.
Bookmakers Bet Victor have installed former Stoke City boss Tony Pulis as the early 7/4 favourite to replace Mowbray.
After 12 games of the season, Boro lie 16th in the Championship on 12 points, with just two wins all season.