The 31-year-old might have played his final game for the Owls.
An own goal from Michael Turner sent them on their way, before George Saville doubled the lead on 34 minutes to give the hosts a 2-0 half-time lead.
Lewis McGugan converted a last-minute penalty to give Wednesday a sliver of hope, though it was too little too late, but Wednesday boss Carlos Carvalhal will care little about the result after naming an under-strength XI for the trip to Molineux.
For Wednesday, the focus is on promotion and Carvalhal's boys will face Brighton & Hove Albion in a two-legged playoff tie as both sides battle to reach the final.
Semedo, who joined the club in 2011 on a Bosman from Charlton, is unlikely to be involved against the Seagulls. In fact, the defeat at Wolves might have been his last game in an Owls shirt, having only started two games this calendar year.
It is no secret that the 31-year-old has a strong and mutual affinity with the club's fanbase, with supporters recognising his heart and industrious showings down the years, and the Portuguese international admits that it was the fans who sent him over the edge.
"It's impossible not to be emotional at the end of the game and see all the fans screaming your name," he said to the club's official YouTube channel.
"The love they show to me is something special and something unforgettable."