Despite Mikel Arteta’s decision to drop captain Pierre-Emerick Aubameyang to the bench for disciplinary reasons, Arsenal started the better of the two sides as Emile Smith Rowe rattled the crossbar.
Spurs were slow starters and lost Heung-min Son to injury early on, but his replacement Lamela lit up the match with what will surely go down as one of the great north London derby goals.
Sergio Reguilon cut back a cross for Lucas Moura, who teed up Lamela in the box – and the Argentine found the far corner with a stunning Rabona effort, wrapping his left boot around his right leg to finish in style 33 minutes in.
Spurs had been up against it before the goal, and Cedric Soares soon went close for Arsenal as he rattled the post with a fierce drive from outside the box.
But Spurs’ luck ran out a minute before half-time as Kieran Tierney beat Matt Doherty on the left flank to cross, and Odegaard’s effort deflected past Hugo Lloris for parity.
Arteta subtituted off Bukayo Saka for Nicolas Pepe at the interval, while Mourinho made a bold call not long after as he brought Gareth Bale off despite Son having gone off injured earlier on.
That switch came back to bite Spurs as Arsenal then took the lead from the penalty spot 64 minutes into the derby. Lacazette was put through on goal but misckicked his volley at the vital moment – though Davinson Sanchez’s attempt to block the shot wiped out the forward, with referee Michael Oliver pointing to the penalty spot.
Lacazette coolly converted to put Spurs up against it, while Lamela’s day turned sour as he was sent off for a second booking after catching Tierney in the face.
Down to 10 men, Spurs tried to fight back and saw a Harry Kane header correctly ruled out for offside and hit the post with a late free-kick, while Gabriel headed the rebound off the line to deny the visitors a late leveller.