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.
A statement on their official website 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 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.”
Mowbray has been unable to guide Boro out of the Championship in his three seasons in charge.
He finished 12th, seventh and then 16th last season, while things are panning out little better during the current campaign.
Boro have won just two of their opening 12 league games and lie 16th in the standings. They went down 3-2 at struggling Barnsley on Saturday and host Doncaster on Friday night.
After the Barnsley game Mowbray signalled he was willing to accept the criticism that came his way. “I can take it. As a football manager in an era of social networks and radio phone-ins you have to because everyone has an opinion,” he said. “You live with it every day now that there’s a platform and I am absolutely fine with that.
“The players didn’t capitulate against Barnsley despite being 3-0 down at half-time [the match ended 3-2] so I think they still believe in what we are doing here. And with the supporters, there has been both positive and negative reaction from them and I don’t think there’s a manager in the world who has total support of his club’s fans.”
However, despite Mowbray’s willingness to soldier on, it would appear the board’s patience ran out.
Bookmakers were keeping an open mind as to who will be chosen to replace Mowbary. Tony Pulis was installed as early 7-4 favourite, with Alex McLeish, Nick Barmby and Martin O’Neill also prominent in the betting.