Liverpool's Alex O'Hanlon, Everton's Jordan Thorniley and Leicester's Elliot Percival joined Burnley's Nathan Lowe in the Owls' squad which beat Sheffield United at Hillsborough.
Goals from Caolan Lavery and Jack Stobbs gave Wednesday a 2-0 win over a Blades team containing first-team stars Louis Reed, Terry Kennedy and Diego De Girolamo.
Midfielder O'Hanlon, who Liverpool Under-21s boss Michael Beale previously described as having "Premier League quality", and full-back Percival were both involved in the Owls' goals.
Defender Thorniley and midfielder Lowe appeared in last week's 0-0 draw against Millwall, with the latter also appearing in a 1-0 defeat to Ipswich earlier this month.
Wednesday have handed run-outs to a number of hopefuls over the past month or so, with the under-21 season set to reach its climax.
Tottenham Hotspur midfielder Charlie Hayford, Chelsea full-back Kevin Wright and Leeds United striker Luke Parkin have all appeared for Neil Thompson's side in that time.