Rams teenager Jeff Hendrick hit the winning goal midway through the second half to leave former England boss McClaren still searching for his first home win in the Championship.
Frank Fielding's second-minute red card provided a dramatic start. Ishmael Miller latched on to a flick inside the Derby box and was clattered by the onrushing Fielding as he bore down on goal just six yards out.
Referee Scott Mathieson had little choice but to send off the England Under-21 goalkeeper.
There was a delay before Andy Reid could take the resulting penalty while Derby reorganised.
Adam Legzdins came on in goal for his first league appearance of the season. Tomasz Cywka, on his first league outing and first start of the campaign, was the unlucky man to be sacrificed.
Legzdins was sent the wrong way from the spot by Reid who claimed his first goal since rejoining Forest in the summer.
The manner of Derby's equaliser in the 29th minute was just as dramatic.
As Forest full-back Chris Cohen lay injured on the ground midway inside the Derby half, following an innocuous-looking clash with Mark O'Brien, the visitors worked the ball out to Jamie Ward on the left wing amid a chorus of boos from the home supporters, calling for play to stop.
Ward evaded a challenge from Radoslaw Majewski to reach the byline, where he knocked the ball around Wes Morgan and collected it on the other side of the burly centre-half before squeezing a low shot past Lee Camp from an acute angle.
Immediately afterwards, Cohen gingerly made his way off to be replaced by Joel Lynch.
Little else occurred in the first half. Miller headed a half-chance wide for Forest between the two goals and Ward did likewise for the visitors just before the break.
McClaren's men started the second half brightly. Reid twice went close, once with a free-kick from the edge of the box, and Miller forced Legzdins to smother a low shot before the hour mark.
But it was Derby who should have taken the lead in the 64th minute. Ben Davies' pinpoint cross from the right was met at the far post by the unmarked Hendrick but the young midfielder somehow headed wide from three yards.
Nathan Tyson swapped the City Ground for Pride Park in the summer and the forward was given a frosty reception from the home supporters on his return when he was introduced as a substitute soon afterwards.
Hendrick then made amends for his earlier miss when he blasted home the winning goal after 72 minutes.
Forest failed to clear a corner and the ball broke to the teenager who fired a right-footed shot into the bottom of the net from 25 yards.
Legzdins preserved his side's lead by pushing away a fierce volley from Lynch with 10 minutes remaining.
Forest piled on the pressure late on but could not find an equaliser. Captain Luke Chambers went closest when he volleyed over from the right side of the box in injury time.