The England Under-21 international enjoyed a loan spell at Hillsborough last season, scoring once in six appearances in a 1-0 victory at Leicester City.
Wickham has been granted the move - which runs until the new year - in order to gain valuable first-team action, after failing to break into the starting XI at the Stadium of Light this season.
The 20-year-old began his career at Ipswich Town before joining Premier League side Sunderland in reported £8million deal in 2011.
Wednesday have been looking to bolster their front line to add to their options which include Atdhe Nuhiu and Matt Fryatt, who extended his loan deal from Hull City last week.
And Wickham could feature as early as Saturday's home fixture against Reading for Dave Jones' men.
"I'm really pleased to come back to Sheffield Wednesday," he told the club's official website.
"There was interest from other clubs but I feel I have unfinished business here and I can't wait to get started again.
"I know the managers, I know the players and the place and that was a big influence in my decision."
Wednesday currently prop up the Championship table, and have yet to register a league victory from their 12 league fixtures.
