It was a mistake from Rovers goalkeeper Christopher Dilo just before the hour mark that handed all three points to the visitors, as the Frenchman mis-controlled a backpass that allowed Bradley Fewster to score the only goal of the game.
It was a match in which Rovers had the better of the chances throughout but they came up short in being able to find a way past the impressive 'Boro stopper Jayason Leutwiler.
It was the visitors who started the stronger on a wet evening at Ewood, England youth striker Bradley Fewster testing the Rovers back line early on with a shot that was saved by the shins of Christopher Dilo.
Then from a free-kick to the back post Ryan Brobbel saw his shot claimed by the Rovers goalkeeper low down.
Rovers were struggling to cope with Middlesborough's passing play, particularly through the middle as it took a last ditch challenge from defender Peter Wylie to prevent Jordan Jones from getting his shot away at goal.
As the first half wore on Rovers started to gain ground themselves, Anton Forrester mis-timing a header when well placed from a John O'Sullivan free-kick before Jamie Maclaren was wide after trying his luck from distance.
It was a strong end to the half for Rovers as a Tom Brown shot was diverted goalwards by Maclaren but the ball went the wrong side of the post into the side netting.
The home side took that strong end to the half into the second period, Anton Forrester showing good pace to race through only to be thwarted by Leutwiler moments after the restart.
The Swiss stopper was then called upon twice more in quick succession, firstly pushing behind a smart shot from John O'Sullivan before from the resulting corner kick he somehow kept out Forrester's header from point-blank range.
However on 58 minutes all of Rovers' good work was undone by a catalogue of errors as Middlesbrough took the lead.
Peter Wylie slipped in possession which resulted in a backpass that Christopher Dilo failed to deal with and 'Boro striker Bradley Fewster needed no second invitation in tapping the ball into an empty net.
Two minutes later and it was almost 2-0 when from a Cameron Park corner kick Christian Burgess put his header just past the post.
From then on it was all Rovers as they looked to get back into the game, Anton Forrester going close once more with a header from a corner that flew inches over the bar.
Then as the match approached the ninety Jordan Slew was denied at the near post, his well-struck shot beaten away by Leutwiler who then denied Maclaren on the follow-up.
Any chance of a late equaliser ended when Rovers finished the match with ten men as Hugo Fernandez saw red for a petulant kick off the ball.
It was a poor ending to a match which Rovers deserved more than they got.
"I thought they were better than us in the first half," said Reserve team coach Colin Hendry. "They had a better quality about them.
"We came into it in the last 15 minutes of the first half and within 20 minutes of the second half we had five or six good chances.
"I was thinking just score the first goal and lets see what happens because you don't know how the opposition will react. Then of course we give away a suicidal goal, it was a comedy of errors, Peter slips, he passes it back and Chris hasn't dealt with it where generally that is one of Chris's strengths when the ball is played back to him.
"But he didn't deal with it and we go behind, but we didn't capitulate, we kept going and we had several good chances.
"They were a good side, they knock it about well, they play the game the right way, but with the amount of chances we had we should have got something from the game.
"We've worked their goalie and their defenders all night, I thought we deserved a lot more out of the game than we got."
ROVERS: Dilo, Wylie (c), Bauress, Brown (sub R. Hanley 75 mins), Payne, Fernandez, Osawe, O'Sullivan, Forrester (sub Cham 85 mins), Maclaren, Slew.
Subs not used: Raya, Wassi.
MIDDLESBROUGH: Leutwiler, Bennett, Sirrell, Morris (sub Kneeshaw 71 mins), Burgess, Okosieme, Brobbel, Park (sub Waters 61 mins), Fewster, Jones, Williams (sub Rhoden 87 mins).
Subs not used: Ripley, Pereira.
Goals: Fewster 58 mins.