Owls match report: Wolves 2 Sheffield Wednesday 1
A Michael Turner own goal and George Saville's 35th minute strike condemned the Owls' to their fourth consecutive loss at Molineux.
Lewis McGugan grabbed a late consolation from the penalty spot, but Wednesday's four-match unbeaten run came to an end.
But having already sealed a top-six finish, the Owls' campaign is far from over.
Carlos Carvalhal's charges will face Brighton and Hove Albion in the Play-Off semi-finals after the Seagulls were held to a draw in their automatic promotion decider with Middlesbrough.
As predicated, Carvalhal made wholesale changes for the Owls' Championship finale. Lucas Joao was the sole survivor from the team who beat Cardiff City last weekend to book their Play-Off spot.
Academy graduate Jack Stobbs was included in the match-day squad for the first time in two years as Carvalhal rotated his squad, with one eye already on next Friday’s first leg of the semi-finals at Hillsborough.
Keiren Westwood, Tom Lees, Daniel Pudil, Sam Hutchinson and Fernando Forestieri were all rested.
It took Wolves just seven minutes to break the deadlock, with Turner diverting Matt Doherty's low cross into his own net after the hosts had carved Wednesday open down the left flank. It was Wolves' first home goal since March 8 following four successive goalless draws.
Wednesday's much-changed line-up struggled to string anything together early on.
Their first sight of goal came in the 16th minute when Carl Ikeme produced a stunning stop to keep out Lewis McGugan's fierce free-kick.
Aiden McGeady went agonisingly close to levelling things up. The Republic of Ireland international showed lovely footwork just outside the penalty area before seeing his deflected left foot drive drift narrowly off target.
Saville doubled Wolves' advantage in the 35th minute, drilling an unstoppable right foot shot out of Wildsmith's reach after fine play by Doherty again. Moments before his strike, Saville was unlucky to see his shot clip Wildsmith's right hand upright after Wednesday only partially cleared a corner.
After the re-start, the Owls, cheered on by over 4,300 fans, wasted a glorious chance to reduce their arrears. McGeady wriggled his way to the byline before whipping in a lovely cross which was headed over by Atdhe Nuhiu.
Ikeme bravely foiled Jeremy Helan, who enjoyed a loan stint for Wolves earlier this season, after some good build-up play as Wednesday kept pressing.
With 17 minutes remaining, Marco Matias saw his overhead kick go harmlessly wide after a purposeful run and cross by Palmer.
Wednesday deservedly pulled one back in added on time, McGugan slotting home from 12 yards after Doherty was penalised for handling Palmer's teasing delivery.
Carvalhal's men nearly snatched an unlikely equaliser as Helan tested the reflexes of Ikeme before Sasso was thwarted by the Wolves shot-stopper.
Wolves: Ikeme; Iorfa, Batth, Hause, Doherty; Price, Coady, Saville; Henry, Wallace (Le Fondre HT), Mason (Edwards 76). Substitutes: Martinez, Deslandes, Byrne, Hunte, Enobakhare.
Owls line-up v Wolves: Wildsmith; Palmer, Sasso, Turner, Helan; Matias, Semedo, McGugan, McGeady; Joao, Nuhiu (Stobbs 79). Substitutes: Price, Loovens, Hooper, Lopez, Hunt, Bannan.
Referee: Darren Bond (Lancashire)