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, the former West Brom and Celtic boss, 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.
Source: PA
Source: PA