Injury hit Barnsley - in front of Oakwell's biggest crowd for 20 years - made Wednesday fight all the way but superior finishing made the difference.
After a high energy start Danny Nardiello produced a half chance after ten minutes, but Barnsley-born Wednesday keeper Mark Crossley - last week's goalscoring hero against Southampton - made a comfortable save from the deflected effort.
A minute later though it was Wednesday who snatched the advantage.
Striker MacLean managed to hook a pass crossfield from the left as he tumbled under a challenge and Andrews, on loan from Coventry, was in space and rounded Neil Austin to rifle his angled shot wide of Nick Colgan's despairing dive.
Three minutes later Wednesday could have stretched their lead when Madjid Bougherra met Chris Brunt's cross but his glancing header hit the bar.
After the goal Barnsley stepped up the pace. Nardiello twice twisted and turned and might have created an opening, but the first time he shot with Paul Hayes and Grant McCann better placed and then he lost the ball when Martin Devaney was well positioned for a pass.
Devaney latched onto a loose ball and his a wild volley over the top before McCann produced Barnsley's best effort of the half with a super curling free-kick that smacked on to the bar before Robbie Williams crashed a 30-yard shot over the bar.
But Wednesday broke again towards the end of the first half with Austin caught out by Frank Simek, but his shot was blocked by Antony Kay.
And when Wednesday won a free-kick two minutes before the break Brunt hit a fierce drive from 25 yards but it was deflected over.
Reid picked out Devaney in space after 56 minutes and with Nardiello well placed in the middle chipped over instead of drilling a low cross.
But three minutes later a carbon copy move pushed Wednesday into a two-goal lead and out of reach of Barnsley.
MacLean worked hard in the middle and fed out the ball to Marcus Tudgay on the right.
His superbly placed low cross was between the defenders and the goalkeeper and found Brunt cutting in from the left to slot his low shot out of Colgan's reach.
And when Kay slipped after 68 minutes MacLean punished him, nipping in smartly before picking his spot with a crisp low shot .