Noel Whelan nearly came back to haunt his old club after just four minutes when he latched on to a Manel flick, but his strong effort was saved by Scott Shearer.
Coventry took the lead against the run of play on 19 minutes when Gary McSheffrey notched his fourth goal in six starts this season.
A Martin Grainger free-kick from the left was met by Calum Davenport whose header found Stephen Warnock.
Warnock's effort was well saved by Lee Grant, but the rebound fell back to the City man at a tight angle. He opted to square the ball to McSheffrey who finished from close range.
Coventry doubled their lead just after the half-hour mark from another set-piece, this time a Bjarni Gudjonsson corner.
Warnock again found himself in space in the box and headed the ball towards Julian Joachim who, with the ball in the air behind him, did exceptionally well to finish into the top corner.
McSheffrey nearly added to his tally early in the second half when Joachim looked to pick him out in the middle, but Richard Jackson made an excellent last-ditch interception.
The game was already slipping out of Derby's grasp when striker Manel was sent off on the hour mark for a clear punch on Coventry defender Peter Clarke.
Moments later, Derby's man-of-the-match Marco Reich had a free-kick excellently saved by Shearer and the young Scot made an even better stop seconds later from Adam Bolder.
Michael Doyle spurned a glorious one-on-one chance to seal the win for Coventry in the closing stages, but Grant saved well.