Back from injury, Callum Hudson-Odoi took just seven minutes to make an impact, dispossessing Jacob Murphy before firing a low shot from distance beyond the reach of the returning Nick Pope.
No PL side has broken the deadlock more than Forest (20), but the one time they went on to lose after doing so was in the reverse fixture against Newcastle.
Having dominated early possession, Eddie Howe’s men turned the game on its head in the space of two minutes. Making his first PL start of the campaign, 18-year-old Lewis Miley made the most of a set-piece being kept alive, sweeping home from inside the box to level in the 23rd minute.
Still reeling, Forest were then caught out by a swift counter-attack as Isak’s backheel found the marauding Lewis Hall, whose heavily deflected pass looped over Matz Sels for Murphy to tap in.
Hall was involved again when VAR recommended a pitchside check for an Ola Aina handball minutes later. A lengthy review eventually led to a penalty award, allowing Isak to shoot high down the middle, with Sels getting a hand to the effort as both he and the ball ended up in the back of the net.
Just moments later, the visitors were caught cold again by a relentless Newcastle, with an incisive breakaway leading to Isak’s shot finding the net via a Murillo deflection.
A close-range stop from Sels denied Murphy before the break, yet a way back into the contest looked fanciful for Nuno Espírito Santo’s side, who were perhaps fortunate not to concede a fifth when Fabian Schär’s looping header struck the post after the restart.
However, an improved period saw the away side threaten through Anthony Elanga’s miscued volley, shortly before Nikola Milenković reduced the deficit via an improvised flick.
At that stage, momentum was well and truly with Forest, and with FT fast approaching, Schär’s goalline block dropped to Ryan Yates, who turned home to set up a grandstand finish. Ultimately, four goals conceded in the space of 11 first-half minutes had done its damage as Forest came up short.
After falling behind, Newcastle’s emphatic response ultimately prevented a fourth loss in five PL games, keeping Howe’s side well in the hunt for a return to UEFA Champions League football, with the Magpies climbing to fifth in the table, three points behind third-placed Forest.