The Owls lost out 3-2 in an eventful encounter against Bristol City, who twice came from behind to leave Hillsborough will all three points.
Miguel Llera’s early goal was cancelled out by Sam Baldock’s spot-kick in the first half.
Gary Madine then put Wednesday ahead in the 78th minute but two goals in the space of three minutes - the first another penalty - from Baldock and Albert Adomah gave the visitors the victory.
The Owls set up with a 4-4-2 formation which saw Madine and Chris O’Grady leading the attack.
David Prutton made his first start at Hillsborough this season after returning from a successful loan spell at Scunthorpe.
Wednesday started brightly and took the lead inside just three minutes. Llera met a Chris Lines corner and headed the ball firmly past Tom Heaton to give the home side the perfect start.
The Owls were dominating the early stages and Madine had an opportunity to double the lead on ten minutes but his low finish was smothered by Heaton.
Michail Antonio then charged down the wing before cutting back to O’Grady, who just failed to get a clean connection and the ball whistled over the crossbar.
The visitors were given a way back into the game on 18 minutes when the referee judged that Llera had fouled Baldock in the area. The same man stepped up and calmly converted the penalty to level the score.
At the end of the first half, Antonio came close to regaining the Owls’ lead with a curling shot from the edge of the area that bounced just inches wide of the post.
Madine had a good chance to put Wednesday back in front at the start of the second period when the striker got on the end of an O’Grady cross but Heaton again came to the rescue to keep the game level.
On 78 minutes, though, the Owls went ahead. Jermaine Johnson charged forward, cutting through a number of challenges before firing at the goalkeeper.
Heaton palmed the ball into the path of Madine, who struck home from six yards to make it 2-1.
But the Owls’ elation was short-lived as Bristol City were awarded a second penalty for handball against Madine. Baldock smashed past Chris Kirkland to grab his and City’s second goal of the game with five minutes left to play.
Just two minutes later the game was turned on its head. Adomah curled beyond Kirkland directly from a free kick to put the visitors in the lead for the first time in the match.
There was yet more drama in the final minute when Madine looked to have grabbed a point for the Owls before the referee disallowed the goal and Wednesday’s woe was complete.
Owls: Kirkland, Buxton, Taylor, Antonio, Lines, Madine, J Johnson (Mayor 81), O’Grady (Rodri 81), Helan, Prutton, Llera
Unused substitutes: Bywater, Maguire, Mattock, McCabe, Lee
Bristol City: Heaton, Foster, Fontaine, Baldock, Taylor, McManus, Elliott, Bryan, Adomah, Danns, Bates
Unused substitutes: Gerken, Wilson, Kilkenny, Pearson, Anderson, Reid, Wilson