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The result means that Nigel Pearson's men will be guaranteed Premier League football for next season, if Queens Park Rangers lose to Bournemouth tomorrow.
Leicester had already threatened through Knockaert, who sliced wide when arriving deep to meet David Nugent's cross, before Mahrez found the net for the third time since signing in January.
Wood provided Nugent with a similar opportunity which the striker failed to curl inside the post and Knockaert also shot wide, but Wednesday were also threatening in an open contest.
Antonio, who was returning to the side following 10 matches out with injury, gave Leicester a warning of what he was capable of when he ran across the box to shoot powerfully at Kasper Schmeichel.
The Foxes did not react to his threat coming in from the left wing, and gave him too much space to drift inside and create room for a 37th-minute shot which crept in despite a strong Schmeichel hand.
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Liam Palmer had a shot blocked by Wes Morgan as the visitors failed to make the most of a promising break and with the Owls in fine form, it took a special strike from Knockaert for Leicester to regain the lead.
Kieran Lee's foul on the edge of the box gave the Frenchman the free kick from which he whipped a left-footed shot over the wall and past Kirkland for his fifth goal of the season.
Wednesday continued to give as good as they got after the interval at the King Power Stadium, where Leicester have been rampant this season, picking up more home points than any other side in England.
When Chris Maguire was picked out on the edge of the box from a corner, he struck across the ball, but generated just too much slice on his shot for it to sneak inside Schmeichel's post.
The Danish goalkeeper was later called upon to save well from Lee, and Wednesday felt that they should have had a penalty when Morgan bundled over Maguire in the goalmouth scramble that followed.
Leicester hung on to move 10 points clear of Burnley, while the result leaves the Owls 14th.