Paul Smith helped Wednesday secure their first home win of the season as the Hillsborough side struck twice in a lightning five-minute spell.
Smith, signed from Hartlepool in the summer, hit the opener in 56th minute and then set up Terry Cooke as Chris Turner's promotion favourites finally got off the mark at Hillsborough.
Wednesday were almost caught out in the opening half from a Gareth Roberts free kick. The Tranmere full back picked out skipper Graham Allen whose fierce header from eight yards crashed against the Wednesday bar.
New signing Adam Proudlock latched onto Derek Geary's deflected cross to drill in a low shot, stopped on the line by John Achterberg, and minutes later he was celebrating as he finally beat the Tranmere keeper only to have the goal ruled out for offside.
The woodwork saved Tranmere a minute before the interval as Cooke found himself in space on the right wing. The ex-Manchester City winger pumped a cross to the far post as Paul Smith connected, his header beating Achterberg as the ball cannoned off the bar.
Wednesday snatched the lead in the 56th minute, the impressive Cooke setting up the goal. His deep cross was only half-cleared and Smith finished with a ferocious left-foot shot from 18 yards.
The Hillsborough side went close just 60 seconds later, Proudlock's cross from the right was pushed away by Achterberg as Lloyd Owusu waited to pounce.
Wednesday's second came on 61 minutes with Smith again involved. The Wednesday midfielder's cross was only half-cleared and Cooke popped up at the far post to head past the Tranmere keeper.
Kevin Pressman pulled off two stunning saves in the dying minutes as Tranmere looked for a way back.