Holloway has never been a winner at Northampton, either with Rangers or former club Bristol Rovers, and the double bogey continues as QPR crashed to their second 3-0 loss in four days - just 30 miles from the scene of their tame folding at Coventry on Saturday.
At least Rangers had the excuse of making five changes to their starting line-up, resting key striker Paul Furlong in the process.
For Northampton, this was a welcome departure from a frustrating league start as it gave them a first win of the campaign at the fifth attempt, although manager Colin Calderwood would gladly swap it for points.
It also gave the Cobblers a Championship scalp in the first round of this competition for the third year running.
After knocking out QPR in 2002, they followed up with Norwich and Gillingham.
This match hinged on the sending off of centre-back Ian Evatt in the final minute of the first half.
Rangers were already trailing to Andy Kirk's 19th minute lob at the time after the ball struck Ugo Ukah on the back of the head and bounced into his path.
Evatt was adjudged to have pulled back Kirk as he threatened to dash through and referee Andy Hall had no option but to show the Rangers player the red card as the last line of defence.
The Cobblers made it 2-0 in the 62nd minute when Scott McGleish bagged his first of the season with an overhead kick from a Josh Low free-kick, and after Eric Sabin had struck a post with two minutes left, the same player was brought down by Ukah at the death allowing him to stroke home the resultant penalty.