The Bees, trailing to a Steve MacLean goal after defender Michael Turner had been sent off, were back on level terms in the 81st minute through substitute Alex Rhodes before striker Deon Burton grabbed the winner 60 seconds later.
Wednesday, whose run of three successive wins ended in defeat against promotion rivals Hull in midweek, failed to break down a stubborn Brentford back four in the opening minutes.
The game came to an abrupt halt for the unfortunate centre back in the 21st minute after centre-back Patrick Collins pumped the ball up field.
His precise pass fell nicely for Lee Peacock, back again after a three-month injury lay off. The former Bristol City striker lined up the shot and had his legs pulled from underneath him by Turner.
The big defender was immediately red carded for a professional foul as MacLean stepped up to stab in the penalty sending Stuart Nelson the wrong way as he tucked the ball to his right.
The hard working Glenn Whelan fired over the top with Wednesday desperate for a second goal.
It almost came as 18-year-old Joey O'Brien, on loan from Bolton, surged through the middle but his shot was too close to Nelson as he sprinted off his line deflecting the ball wide of the target.
Bees boss Martin Allen was banished to the stands in the 48th minute before Chris Brunt was inches away with his curling free-kick leaving Nelson stranded on his line as the ball flashed the wrong side of the target.
Lee Bullen saw his flashing header tipped over by Nelson and Brunt slammed the ball into the side netting before Brentford snatched a dramatic late victory.