The young Foxes came into the cup tie unbeaten in four Premier League U18 South games and six changes were made to the side that drew 1-1 with Crystal Palace last Saturday.
Chituru Odunze, Azeem Abdulai and Oliver Ewing all returned after featuring for the Development Squad against Chelsea Under-23s on Monday.
Following a cagey start, the visitors fashioned the first opportunity of the contest. Basile Zottos got to the byline and found Wednesday captain Alex Bonnington free in the middle, but Odunze got down quickly to tip the ball past the post.
From Leicester's first attack, they went ahead. Wanya Madivadua was simply too quick for the Wednesday backline and his speedy run was matched by a finish into the bottom corner.
The visitors thought they had levelled on 10 minutes when Corey Graves headed in Jay Glover's free-kick, but the assistant referee's flag was up to rule out the equaliser.
City quickly turned defence into attack as Ethan Fitzhugh carried the ball forward and played Kian Pennant through, though Alexander Hare was out quickly, producing a strong hand to stop the strike.
Madivadua came close to his second of the night thanks to more good work from Fitzhugh, finding the winger in space on the right but he was unable to find the target once more, striking wide of goal.
Leicester controlled possession for the rest of the half and just after the half hour mark, found the second goal that their performance deserved. Kian Pennant got in front of his marker to head home Sammy Braybrooke's corner at the near post.
There were still moments of danger from the away side, once again created by Zottos, but Paulo Aguas' shot was hit into the ground and came back off the crossbar.
Madivadua and Tawanda Maswanhise both had efforts that Hare had to deal with, before the Wednesday shot-stopper used his legs to beat away Fitzhugh's low attempt, following nice work from Brandon Cover and Madivadua.
Fitzhugh would get his goal two minutes before the break, exchanging a one-two with Madivadua before firing in a first-time hit into the bottom corner, putting City in full control at half-time.
The second half initially followed a similar pattern and Fitzhugh could have grabbed a second when he struck straight at Hare, following Madivadua's cut-back.
Odunze had to be alert at the other end, spreading himself to keep out Bonnington, who was bearing down on goal. Wednesday continued to look for a route back into the contest and almost found it when Aguas was denied by Odunze, before Harvey Godsmark-Ford cleared his second attempt off the line.
Glaves then saw his header from Glover's corner tipped over at full stretch by City's 'keeper, preserving the clean sheet, though he could only watch as Luke Hall tried to place the ball in the corner, narrowly missing the target.
Foxes skipper Ewing picked out Maswanhise and weaved through several challenges before firing high and wide as City looked to reassert their dominance.
Madivadua then bagged his brace on 68 minutes, applying a calm finish as he rolled the ball past Hare after using his pace to get in behind the defence.
Kian Pennant would also find the net for a second time, poking home inside the area after persistent work from Jesper Kutshienza on the left wing to provide the assist.
Substitute Will Russ almost added a late sixth but couldn't find the target with a powerful effort, following a strong run to the edge of the 18-yard box, though City had already done enough to secure a safe passage into round four.
Kian Pennant wheels away in celebration after scoring City's second goal.
Leicester were ruthless in attack and the opener, coming after Sheffield Wednesday's early chance, was the perfect start, settling any nerves and allowing them to play their game.
Wanya Madivadua celebrates scoring his first goal of the night.
Wanya Madivadua was a constant threat on the left-hand side, using his pace and trickery to great effect on several occasions, including for both the opening goal and his second, which were both well taken.
Where does it leave us?
Chituru Odunze had to make some smart saves in the second half to maintain a clean sheet.
The reward for their win on Friday evening is a trip to Devon to face Exeter City in the fourth round of the competition.
Ethan Fitzhugh was also on target at LCFC Training Ground.
The young Foxes return to Premier League U18 South action on Saturday 13 March, tackling Brighton & Hove Albion Under-18s at LCFC Training Ground (1pm kick-off GMT).
City: Odunze; Cover, Godsmark-Ford, Abdulai, Kutshienza; Maswanhise (T. Pennant 73), Ewing (c), Braybrooke, Madivadua (Russ 79); Fitzhugh (Wormleighton 61); K. Pennant.
Subs not used: Doherty, Obi, Yfeko, Butterfill.
Goals: Madivadua 6', 68', K. Pennant 31', 78', Fitzhugh 43'.
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