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The Terriers were replaced at the top by a newly-promoted Scunthorpe side brimming with confidence.
This defeat, Huddersfield's first at home in 14 matches, wrecked the club's celebration of boss Peter Jackson's manager of the month award.
The curse of the division's top boss struck again as Huddersfield were humbled.
Huddersfield led the division after last Monday's 2-1 victory at Doncaster, but their reign as League One top-dogs did not last the week out.
The Terriers went behind in controversial fashion in the seventh minute when keeper Paul Rachubka was adjudged to have pulled down Billy Sharp.
Sharp broke into the box but had over-run the ball when he was challenged by Rachubka.
However, referee Carl Boyeson gave the spot-kick and Peter Beagrie sent Rachubka the wrong way.
If that was fortunate there was nothing lucky about Scunthorpe's second in first-half stoppage time.
Huddersfield's 17-year-old defender Tom Clarke slipped and allowed Keogh to race free. He kept his cool and slotted past Rachubka.
Just after the restart Gary Taylor-Fletcher should have given Huddersfield a lifeline, but he scooped the ball over the bar with the goal gaping.
He was rescued by midfielder Chris Brandon, who turned brilliantly only to be tripped by Richard Ryan just inside the box.
Pawel Abbott despatched the penalty for his seventh goal in eight games.
Scunthorpe though were not to be denied and substitute Matthew Sparrow sealed it when he headed home in the 74th minute after Cleveland Taylor's shot came back off the bar.
Jackson's misery was complete seven minutes from time when Keogh added his second with a header from Sharp's cross and Scunthorpe were in dreamland.