Late goals from Bobby Hassell and Andy Gray earned Barnsley a 2-1 victory and left high-flying Blackpool's unbeaten Coca-Cola Championship home record in tatters.
Charlie Adam claimed his seventh goal of the season with a 78th-minute penalty to put the Seasiders on course for victory.
The highly-rated midfielder held his nerve to fire home from 12 yards but the Tykes fashioned a late rally that reaped rich rewards.
Defender Hassell popped up to equalise with five minutes remaining and Gray netted from the spot three minutes later.
Blackpool boss Ian Holloway made two changes to his starting line-up from the side which drew 1-1 with Preston on Monday.
Rob Edwards and Neal Eardley stepped up from the bench to replace the injured Marcel Seip and Ian Evatt, who was forced to settle for a place on the bench.
The Seasiders were dealt a blow after just three minutes when striker Ben Burgess picked up an injury and was replaced by Jason Euell.
Yet they were almost in front two minutes later when defender Neal Eardley collected possession and drove a 25-yard shot narrowly over the crossbar.
In the 12th minute they fashioned an even better opening when an outswinging corner from David Vaughan was greeted by defender Alex Baptiste.
His header from 12 yards out flew narrowly wide of the target but Holloway's men continue to probe and went close in the 14th minute through Euell.
The former Charlton man drilled a right-footed shot goalwards from 18 yards and Barnsley goalkeeper Luke Steele produced a fine save to push the ball around a post.
Midway through the opening period, the visitors came to life when an Adam Hammill's corner was met by Emil Hallfredsson, whose 12-yard strike was well blocked by Baptiste.
The pendulum swung back towards Blackpool in the 25th minute when Algeria striker Hameur Bouazza volleyed wide from 12 yards when he should have done better.
He then fired wide again from distance moments later as genuine goalscoring opportunities remained scarce.
Eardley and Billy Clarke - who wrote his name into Bloomfield Road folklore with a stunning strike in Monday's derby with Preston - both failed to hit the target when well placed.
Blackpool were dealt a second injury blow just before the break when Clarke was forced off and replaced by on-loan Aston Villa youngster Barry Bannan.
Blackpool remained largely dominant after the restart but struggled to make it pay.
They created a clear opening in the 61st minute when Adam burst through the static Barnsley defence and drove a fierce 18-yard shot goalwards.
Steele made a fine parried save and was on hand again to deny Bouazza's follow-up effort.
Yet Blackpool were finally ahead in the 72nd minute when Ryan Shotton handled and Adam fired home left-footed from 12 yards into the bottom right corner.
However, Barnsley were not to be denied and they were level when Hassell nodded in Iain Hume's corner with five minutes remaining.
They snatched the points in the 88th minute when Baptiste was punished for a handball offence and Gray kept his cool to fire into the top corner from the spot.
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