Mowbray, who spent 10 years as a player with the Teessiders, has been handed the reins following last week's departure of Gordon Strachan.
Strachan stepped downwith the pre-season promotion favourites languishing 20th place in the table.
Mowbray, 46, had been out of work since being sacked by Celtic in March. The defender made 424 appearances during a decade with Boro before a £1million move to Celtic in 1991.
The former Hibernian and West Bromwich Albion boss will be assisted at the Riverside Stadium by long-time number two Mark Venus.
Paul Ince, Paul Jewell, Alan Curbishley and Phil Brown were all also linked with the vacancy.