Ivan Toney’s second half header was enough to condemn Barnsley to a first home defeat under Valérien Ismaël.
Unchanged from the weekend’s victory over Nottingham Forest, the Reds couldn’t quite impose themselves against a very strong Bees side and were narrowly edged out by last season’s play-off finalists.
Brentford made a brighter start to the contest and Tarique Fosu stung the hands of Jack Walton in the opening exchanges before Rico Henry rasped a low drive narrowly wide of the upright moments later.
The Reds gradually got into their free-flowing groove and, after a slick passing move, Matty James lashed over having been teed up by Conor Chaplin.
Alex Mowatt then took aim from distance and his swerving shot almost outfoxed David Raya in the visiting goal as he could only parry our skipper’s effort into a dangerous area before a Bees defender hacked clear.
Chances were few and far between at either end, with Barnsley perhaps looking likelier to break the deadlock with their quick counter-attacking football. The ever-adventurous Callum Brittain burst forward and fired a magnificent cross into the area, but Dominik Frieser just couldn’t stretch enough to get a toe on it to prod home.
HALF-TIME: Barnsley 0-0 Brentford
Ten minutes after the restart, Bryan Mbuemo picked the ball up 25-yards from goal and bent a vicious shot just over Walton’s bar as Brentford looked to gain a foothold in the game.
The visitors had the bit between their teeth and came close again when captain Pontus Jansson headed straight at Walton.
Midway through the half, though, Brentford eventually made the breakthrough when former Reds loanee Toney glanced a header into the far corner.
The Bees were in the ascendancy and almost doubled their lead moments later, but Mbuemo blazed over when clean through on goal when it appeared easier to score.
Barnsley rarely threated and, despite making a triple substitution with 20-or-so minutes remaining, those fresh legs were unable to spark new life into a tired side.
However, the hosts should have been awarded a penalty when Victor Adeboyejo outmuscled Ethan Pinnock and fired a cross into the box that struck the arm of Vitaly Janelt, but referee Darren Bond waved away the Reds’ protests.
As the board went up to indicate three minutes of stoppage time, Walton produced a fine block to deny Marcus Forss as Brentford looked to end the tie as a contest.
Despite a late rally, Barnsley were unable to snatch an equaliser and the Bees left Oakwell with all three points.
FULL-TIME: Barnsley 0-1 Brentford
Walton, Sollbauer, Helik, Andersen, Brittain, James (Kane), Mowatt (c) (Oduor), Styles, Frieser (Thomas), Woodrow, Chaplin (Adeboyejo).
Unused: Collins, Moon, Palmer, Miller, Schmidt.