An eventful afternoon at the Gtech Community Stadium began with Ivan Toney seeing his finish disallowed before the former Magpies man's penalty was saved by United custodian Nick Pope.
Toney made no mistake from the spot second time around though as the Bees held a slender half time lead, but United responded superbly after the break to take the points.
Joelinton provided the leveller, finding the target via a touch from Brentford goalkeeper David Raya, before Isak's terrific strike from the edge of the penalty box gave Eddie Howe's side a lead they wouldn't relinquish in what was a classic game of two halves.
Brentford's bright start saw former Newcastle frontman Toney, predictably, probing for chances against his former club and inside the first ten minutes, United were dealt a warning when he had the ball in the back of the net. It came after a fine save from Pope, who did superbly to get down to his left and keep out Pontus Jansson's header, and though Toney was able to turn it home - scooping in from close range - the goal was chalked off following a protracted VAR check.
Had it stood, the hosts would have felt they deserved to be in front, such was the intensity of their start to the contest, while Howe's men lacked their usual zip in the opening exchanges. When Jansson was forced off injured less than halfway through the first period, United grew in stature and began to exert some control, but that promising spell came to an end just before the half hour when the Bees were awarded a spot kick.
The lively Kevin Schade won it for Thomas Frank's side, after taking advantage of Fabian Schär's slip and getting into the box where Sven Botman's mistimed challenge gave referee Chris Kavanagh little choice but to point to the spot. Toney stepped up in his usual unruffled manner but found Pope in top form, with the England stopper comfortably gathering his international teammate's tame low effort to keep his side level.
It was another let-off for the visitors and after another lengthy VAR check when Isak caught Rico Henry, Toney was handed another opportunity to break the deadlock from the spot in the half's dying moments. The call appeared harsh on Isak and Pope went the right way, but just couldn't quite keep out Toney's effort, which was struck more firmly than his first attempt to send Newcastle in behind at the break.
Howe made two attacking changes at half time, introducing Anthony Gordon and Callum Wilson in place of Sean Longstaff and Jacob Murphy, and there was an immediate improvement, with Dan Burn getting a fleeting sight of goal a minute after the restart that was extinguished by the offside flag. It was a positive response from United and nine minutes into the second period, they found a leveller.
It owed much to the industry of Joelinton, who was played in down the right by Kieran Trippier. The Brazilian showed great composure to cut inside his man and, with Raya narrowing the angle, slip a shot under the Spanish stopper and into the net.
The equaliser, which was initially recorded as a Raya own goal, got Newcastle going and seven minutes later they moved in front. Joelinton played it forward to substitute Wilson, who cut inside and rolled a pass into the path of Isak. With 18 yards between the Swede and Raya's goal, he took it first time, curling a wonderful strike beyond the Bees' goalkeeper and into the top corner to complete the turnaround.
Isak almost made it three moments later, seeing two efforts repelled, and from the resulting corner they thought they had a third through Wilson, who saw his goal ruled out for handball after yet another VAR check.
But for all their second half dominance, Newcastle were still indebted to Pope, who produced another excellent save to beat away Toney's header in the final ten minutes. United could have extended their advantage in stoppage time when Wilson and then Elliot Anderson miscued in front of goal, while Toney couldn't keep his header down at the other end, but after a frantic finale Howe's men - who are back in third place - held on to make it five wins in a row.
