Victor Osimhen scored a brace as Galatasaray condemned Tottenham to their first Europa League defeat of the season.
Manager Ange Postecoglou made seven changes from Sunday's win over Aston Villa with three teenagers in Archie Gray, Lucas Bergvall and Will Lankshear included in the starting line-up.
A cauldron of noise greeted the Spurs players for the warm-up and it was even louder when play got under way.
Every touch by a visiting player was whistled but they soon turned to celebrations when Yunus Akgun fired the hosts ahead with a swerving half-volley from 25 yards after Gray partially headed clear a free-kick.
Fraser Forster had to slide in on Osimhen soon after following a poor back pass by Bergvall, but Tottenham regrouped and levelled after 18 minutes.
Gray brought the ball forward and wonderfully chipped over the Galatasaray defence into the path of Brennan Johnson, who squared for Lankshear to divert the ball in at the back post.
It was not the slickest finish from Lankshear as his effort from close range ballooned into the roof of the net, but it was a moment to savour for him.
Spurs' respite did not last long and Osimhen punished them with two goals in eight minutes.
After Forster had produced a fine low save to thwart Osimhen, he had the ball in the net on the half an hour mark but was flagged for offside.
The Napoli loanee would not be denied and scored in the 32nd minute after a gift from Tottenham.
Bergvall initially dallied on the ball before Radu Dragusin was inexplicably dispossessed, which allowed Dries Mertens to send Osimhen away to poke past Forster.
Osimhen then made it 3-1 when he got in behind Dragusin and steered Mertens' cross into the bottom corner.
Postecoglou sent for Rodrigo Bentancur and Dejan Kulusevski at half-time, with Johnson and Son replaced in a nod to Sunday's visit of Ipswich.
It failed to stem the tide as Bentancur blocked Mauro Icardi's effort on the line after Forster dropped a cross before the Spurs goalkeeper atoned with a brilliant stop to deny Osimhen his hat-trick.
Kulusevski fashioned a chance for Lankshear moments later, but he fired straight at Fernando Muslera and his night turned sour after an hour.
Moments after Lankshear was booked for bringing down ex-Spurs defender Davinson Sanchez, he dived into a challenge with Sara by the halfway line.
It left referee Lawrence Visser with a decision to make and he showed the teenage forward a second yellow card, which left Postecoglou bemused.
Nevertheless, the Tottenham boss refused to take a backwards step and brought on Pape Sarr and Solanke for disappointing duo Bergvall and James Maddison.
It worked perfectly as the visitors reduced the deficit with 21 minutes left when Kulusevski threaded into Pedro Porro, who picked out Solanke to back flick beyond Muslera for his sixth goal of the season.
There would be no dramatic finale, though, as Kulusevski sent a long-range effort wide and Spurs suffered a first defeat in Europe this season.
