Neeskens Kebano scored his first goal in a Boro shirt - but Neil Warnock’s side left Derby empty handed.
After failing two down inside the opening half hour, Boro had left themselves with too much to do to take something from the game.
Boro had started brightly. George Saville had an early shot blocked and Darnell Fisher saw an effort deflected into the arms of David Marshall.
The home side took the lead in controversial circumstances inside the opening 15 minutes. Marcus Bettinelli appeared to be floored as a corner was headed back across goal and Lee Gregory was able to head into an empty net.
Neeskens Kebano almost carved out an immediate response but his cross was just too high for Britt Assombalonga to cash in on.
The game was a stop-start affair and Sam Morsy shot wide as Boro looked for an equaliser.
But it was Derby who went 2-0 up after turning defence into attack. Marshall clawed away a Jonny Howson ball aimed for the head of Assombalonga and the Rams went straight up the other end and scored, courtesy of a powerful strike from Colin Kazim-Richards which went in off the underside of the bar.
Boro were back it in before the break though with an equally incisive attack, started by a Marc Bola interception, that ended with Kebano scoring his first for the club with a close range effort.
Warnock’s side enjoyed the territorial advantage throughout the second half, but were unable to force a way back.
The boss handed Nathaniel Mendez-Laing his debut and moved Paddy McNair into a midfield role as he looked to find an all-important equaliser.
Grant Hall went close with a header, Mendez-Laing had a shot blocked and forced a save from Marshall as Boro threw everything at Derby during the final moments.
There was also a penalty shout waved away after Bola went down in the box, but the home side hung on to win 2-1.