Blackburn's European dream was kept firmly alive thanks to a stunning Craig Bellamy brace, on a day when fellow countryman Robbie Savage was shown the first red card of his club career.
Mark Viduka had equalised for the visitors, before Morten Gamst Pedersen restored Rovers' lead with a trademark free-kick. Fabio Rochemback struck Boro's second shortly after Savage's dismissal, but Bellamy's 15th of the season secured Rovers' fifth home win in succession.
Following their giant-killing display against AS Roma in midweek, Steve McClaren made eight changes to his side, Mark Schwarzer, Chris Riggott and George Boateng the only survivors.
Mark Hughes made two changes to the side that defeated Aston Villa a week ago. Former Boro trainee Andy Todd failed to shake off a dead leg and was replaced by Zurab Khizanishvili, while Brett Emerton was preferred to David Bentley on the right.
Rovers started the game well and took a deserved lead on ten minutes. Emerton found Bellamy in the box and, after a quick turn and sudden burst of pace took him past Chris Riggott, the Welshman beat the despairing Schwarzer with a sublime left-footed curler.
On the quarter-hour mark, James Morrison, making his 50th appearance for the Teessiders, almost deceived Brad Friedel with a 30-yard volley, but just a minute later the visitors pulled level.
Lucas Neill's long throw caught out his entire defence and, after Morrison had flicked in Viduka, the Australian fired low past Friedel at his near post.
But the big American atoned for his mistake with a brilliant save just a minute later, before Rovers moved back into the ascendancy.
On 28 minutes, Bellamy raced 50 yards to keep the ball in play, before nut-megging Franck Queudrue to win a free-kick right on the edge of the box. Up stepped Pedersen and the Norwegian did the rest, firing through a crowd of players into the bottom right corner with a crisp left-footed strike.
Middlesbrough made a triple substitution at half-time and it wasn't long before they were only up against ten men. On 52 minutes, Savage was booked for a challenge on Boateng and, just two minutes, later a long ball forward struck the Welshman's arm and he was shown a second yellow card much to the astonishment of the entire crowd.
And it wasn't long before the man advantage took effect. On 63 minutes, Rovers were caught out down the right and, when Morrison's pull-back fell kindly for Rochemback, the Brazilian equalised with a powerful right-footed drive.
But just six minutes later Rovers broke quickly to score what proved to be the winning goal. Pedersen found Bellamy on the right, and from a seemingly impossible position, the former Newcastle man rifled the ball past Schwarzer with a swerving right-footed shot.