Stefano Okaka struck the decisive goal as Anderlecht triumphed 2-1 to inflict a first Europa League defeat of the season on Tottenham at Stade Constant Vanden Stock on Thursday.
Christian Eriksen put the visitors ahead in the Group J clash after just four minutes, but Guillaume Gillet's fine equaliser ensured the scores were level at half-time.
Substitute Harry Kane spurned a great chance to put Spurs back in front and the Premier League side were made to pay just moments later, as Okaka turned in Frank Acheampong's cross with 15 minutes to play to seal the win.
Spurs were unbeaten since September's League Cup loss to Arsenal, but they struggled to impose themselves at times against a high-pressing Anderlecht, who now move level with Mauricio Pochettino's side on four points with three games played.
Hugo Lloris flapped at a cross and Olivier Deschacht headed the resulting corner straight at the Spurs keeper, before Eriksen tested Silvio Proto from 20 yards in a frantic opening exchange.
It was Eriksen who struck the opener, slotting calmly past Proto from 12 yards after Kara's attempted clearance came straight off Leander Dendoncker's face and fell kindly into his path.
Eriksen teed up Erik Lamela for a glorious chance for a second, but the Argentina winger fired straight at Proto when unmarked inside the area, with Spurs left to rue that miss as Anderlecht hauled themselves level.
Steven Defour's corner bounced through the box to Gillet, who took a touch before firing a half-volley through the crowded area and into the bottom-left corner.
Okaka failed to connect properly with Imoh Ezekiel's cross from right in front of Lloris, and the France number one had to be alert to beat away Okaka's strike from 18 yards out after Spurs failed to clear a free-kick.
Lamela prodded past Proto only for the offside flag to come to Anderlecht's rescue, before Okaka again tested Lloris with a low drive from 25 yards out as a thrilling first half finished level.
Lloris was by far the busier keeper at the start of the second half, reacting superbly to deny Okaka after his header bounced awkwardly through the six-yard box.
Anderlecht looked the more likely to break the deadlock, but substitute Kane spurned a great opening for Spurs, shooting straight at Proto after holding off Kara inside the area.
Okaka had been impressive throughout and the Italy striker was rewarded with the winning goal thanks to some dreadful Spurs defending. Acheampong ran clear in behind Kieran Trippier and squared for Okaka, who finished high past Lloris despite Jan Vertonghen's best efforts.
Dendoncker headed just wide of the near post from a corner and Dennis Praet was denied on the goal-line by Lloris, but, despite late Spurs pressure, Anderlecht held on for their first win of the Europa League campaign.
