Robbie Mustoe condemned Derby to their third successive defeat and pushed the club closer to the Nationwide League.
The Middlesbrough midfielder grabbed the winner after 13 minutes at Pride Park.
Derby huffed and puffed in an effort to get back in the game but lacked the class or the clout to turn things around.
It was deeply frustrating for manager John Gregory, who paced the touchline, most of the time with his head in his hands.
He recalled Lee Morris to the starting line-up in preference to Giorgi Kinkladze following the defeat by Chelsea.
Middlesbrough had to do without striker Alen Boksic, who picked up a knock in the draw against Tottenham.
Derby won a free-kick on the left after six minutes and Simo Valakari delivered a ball to the back post.
Chris Riggott made a good run from deep but the cross was marginally over-hit and he was unable to make contact.
Derby found themselves under pressure in the 10th minute when Luke Wilkshire whipped in a cross from the right.
Defender Warren Barton was alert enough to divert the ball for a corner.
Derby keeper Andy Oakes then did well to punch away an inswinging corner from Benito Carbone.
Middlesbrough made the breakthrough in the 13th minute after a moment of hesitancy from England Under-21 defender Riggott.
He lost possession to Mustoe, who took full advantage to sweep the ball home with a fine volley.
Derby were playing with the kind of fear that goes with being near the foot of the table.
Gregory was continually frustrated as passes went astray and his side showed little penetration or movement.
Wilkshire was finding plenty of room on the right for Middlesbrough and Barton had to make a hurried clearance from another decent delivery.
Gareth Southgate got on the end of Carbone's corner, only to steer his header wide.
Derby almost drew level in the 40th minute when Rob Lee smashed in a volley but keeper Mark Crossley reacted instinctively to parry it clear.
Middlesbrough hit back and a poor clearance from Oakes fell to the feet of Franck Queudre.
He was unable to find the power or the direction in his low shot to make the keeper pay.
It was a worrying time for Derby boss Gregory with his team facing an uphill battle in the second half.
He knew he needed a vastly improved performance from his side in the last 45 minutes if they were to turn things around.
The Derby supporters had become increasingly frustrated as the game unfolded.
Gregory decided it was time for desperate measures and brought off his main strikers Fabrizio Ravanelli and Branko Strupar.
Malcolm Christie, who has been sidelined with a hamstring injury, and Kinkladze were called up.
Morris moved up to partner Christie in a new front-line partnership, with Kinklazde occupying the vacant slot in midfield.
Kinkladze picked out Morris in the 50th minute with a good cross but his header failed to trouble keeper Mark Crossley.
Carbone was then left limping after a stiff challenge by Rob Lee that went unpunished.
Derby were beginning to win a bit more possession but Ugo Ehiogu and Southgate were both looking comfortable at the back for Middlesbrough.
Gregory was no doubt hoping Christie's pace would trouble the opposition but the service to the England Under-21 international was poor in the early stages of the second half.
Christie and keeper Crossley both needed brief treatment when they challenged for a long clearance from Riggott.
Middlesbrough were content to sit back and try and hit Derby on the counter-attack.
The policy almost paid off in the 66th minute when Jonathan Greening got clear down the left and delivered a good ball into the area, only for Luciano Zavango to make a timely clearance.
Derby were beginning to find openings and Paul Boertien found space to get on the end of Barton's cross but his header drifted wide.
Kinkladze then sent a volley wide but Middlesbrough went to onto secure the points and a place in the top half of the table.
Teams:
Derby: Oakes, Barton, Riggott, Higginbotham,
Zavagno (Elliott 83), Valakari, Lee, Boertien, Morris,
Ravanelli (Christie 45), Strupar (Kinkladze 45).
Subs Not Used: Foletti, Grenet.
Booked: Barton.
Middlesbrough: Crossley, Stockdale, Southgate, Ehiogu, Queudrue, Wilkshire, Ince, Greening, Mustoe, Carbone, Whelan.
Subs Not Used: Beresford, Festa, Windass, Marinelli, Johnston.
Goals: Mustoe 12.
Att: 30,822
Ref: P Durkin (Dorset).