The scoreline was level at half-time as the Magpies twice came from behind. But the Eddie Howe’s side struggled to get a grip of the game in the second-half as Nathan Collins and Kevin Schade handed the home side three points.
Howe made two changes from Wednesday’s 3-3 draw with Liverpool at St James’ Park. Anthony Gordon and Sandro Tonali were rested and replaced by Harvey Barnes and Sean Longstaff.
Longstaff saw a shot cannon off the crossbar in the opening exchanges before Bryan Mbeumo handed the home side the advantage in the eight minute. But United immediately responded when Jacob Murphy left-footed shot was diverted home by Isak for his seventh goal of the campaign.
The Sweden international then squandered a major chance moments later when he dispossessed Nathan Collins and rounded goalkeeper Mark Flekken, however the striker dwelled on the ball allowing Flekken to recover.
That missed opportunity came back to haunt the Magpies when Yoane Wissa made it 2-1.
It was Barnes’ misplaced pass that led directly to Wissa’s strike but the winger quickly made amends when he was found in space in the box by Murphy to fire the ball into the bottom left corner.
The game was nicely poised at half-time but Howe’s men didn’t turn up. They fell behind Flekken’s long punt made its way to Collins before substitute Schade put the result beyond doubt in the 90th minute.
Newcastle remain 12th in the Premier League table.
Our writer Jordan Cronin was at the Gtech Community Stadium - and here are his Newcastle United player ratings:
1. Nick Pope - 6
Conceded three goals but could do little about them. Pulled off an outrageous save when Yoan Wissa’s cross was deflected goalwards by Tino Livramento as he somehow tipped the ball onto the post. Almost gifted Bryan Mbeumo a late goal. | Getty Images
2. Tino Livramento - 5.5
Showed great energy and athleticism to drive Newcastle forward at various points of the game. Slipped as Kevin Schade made it 4-2. | Getty Images
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3. Fabian Schar - 3.5
Switched off in key moments. Gave the ball away cheaply at times that put Newcastle under pressure and allowed Mark Flekken’s long put to float over his head as Brentford made it 3-2. Lackadaisical. | Getty Images
4. Dan Burn - 5.5
Pulled out of position on more than one occasion and wasn’t as dominant in the air as hoped. But kept going as Brentford attacked for most of the second-half and cleared a late effort off the line. | Getty Images