Young midfield duo Michael Jacobs and Jeff Hendrick did the damage with first-half goals before Conor Sammon scored midway through the second half to seal the three points and keep the Rams well positioned to mount a play-off challenge in 2013.
Boro arrived at Pride Park having won four of their last five league games but Tony Mowbray's team suffered an off-day in the east Midlands.
Middlesbrough created very little and the margin of victory for Derby might have been greater, with a Ben Davies free-kick striking the crossbar and Jason Steele saving when one-on-one with Sammon.
The visitors did pull a goal back in injury time through Lukas Jutkiewicz but it was too little, too late.
Jacobs had a goalbound effort blocked by Jonathan Woodgate and saw a 20-yard shot narrowly miss before getting on the scoresheet in the 19th minute.
Davies picked out Jacobs just inside the box and the 21-year-old confidently stroked a right-foot shot into the bottom corner of the net.
Hendrick flashed a shot inches wide shortly afterwards before the 20-year-old found the target after 42 minutes, sending a screamer of a shot into the top right-hand corner of the net from the edge of the area.
The third goal finally arrived after 65 minutes. Another of the Rams' impressive youngsters, Will Hughes, showed good feet in the penalty area before Jacobs' shot was saved by Steele and Sammon was on hand to tap home the loose ball.
Home keeper Adam Legzdins was called into a rare piece of action with 15 minutes remaining, pushing away Ishmael Miller's stinging shot.
Substitute Miller did make a difference when he came on and it was he who set up Jutkiewicz for a tap in in the second minute of added time with a cross from the left wing.