Clarke, 23, was a product of the Molineux youth academy and made 74 appearances before moving to Hillsborough 18 months ago.
With Akpo Sodje ruled out by the knee injury suffered on the opening day against Burnley, Clarke will start in attack as t
he Owls look to stay top of the table.
"It's a massive game for Leon as he's playing his hometown club." said manager Brian Laws. "If anybody is going to be up for this game, it's him."
Despite the kudos associated with holding top spot in the Championship, Laws is keeping his first firmly on the ground.
"It's only one game – we'll look at the league table after 10 games and, if we're still up there then, fantastic," he said. "The most important thing is we have the monkey off our back. We lost the first six games last year, but now that is eradicated because of last week's performance and we want to take our confidence into the next game."
Wolves were held by Plymouth Argyle on the opening day of the season and needed extra time to get past Accrington Stanley in the first round of the Carling Cup.
But Laws points to the £30m that has been invested in the side by owner Steve Morgan as proof that they should be regarded as serious contenders in the play-off race.
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