Jefferson Farfan pounced on an error from Tottenham debutant Gilberto to hand PSV Eindhoven a crucial first-leg lead in their Uefa Cup last-16 match.
The Peruvian took the ball off the Brazilian 25 yards from goal, drove into the box and then fired past Paul Robinson brilliantly on 33 minutes.
It rewarded a fine display from PSV, who could have won by more had Farfan not wasted three other great chances.
Robbie Keane had Spurs' best effort, but keeper Heurelho Gomes saved well.
The defeat was only Tottenham's third in 59 European matches at White Hart Lane, and leaves them with an uphill struggle when they visit the Eredivisie leaders in a week's time.
Spurs began the night by parading the Carling Cup trophy in front of the home fans.
606: DEBATE
And Juande Ramos provided them another fillip with his team selection - Ledley King, Jonathan Woodgate, Jermaine Jenas, Aaron Lennon, Robbie Keane all returning to the starting XI following Saturday's 4-1 drubbing to Birmingham.
However, PSV have been involved in European competition far more than Tottenham in recent years and their greater experience was evident throughout the first half.
The Dutch side, who are leading the Eredivisie by six points, were happy to sit and soak up Tottenham pressure and attempt to hit their opponents on the break - and it worked a treat.
Despite dominating possession, Spurs failed to really trouble Gomes in the PSV goal until the 38th minute - and by that stage they were already a goal down.
Gilberto was at fault, needlessly gifting Farfan possession 25 yards out as PSV broke and the striker strode on and finished brilliantly past Robinson.
It capped a nervous first half from the Brazilian, who had only prevented an earlier Farfan charge on goal with a cynical foul that deservedly earned him a yellow card.
The goal did at least spark some attacking fervour from Tottenham, with Steed Malbranque seeing a firm shot deflected wide and then a volley minutes later palmed wide by Gomes.
And Keane almost brought the hosts level with a sublime piece of skill, controlling Robinson's long punt and holding off two defenders only to see his left-foot shot palmed away.
But the second half followed much the same pattern as the first, and Ibrahim Afellay should have made it 2-0 when he sliced wide from 20 yards.
It was proving a thoroughly professional European display from the Dutch giants and matters took a turn for the worse for the hosts when Jermaine Jenas was stretchered off with a twisted ankle.
Spurs boss Ramos mixed things up with 20 minutes left, replacing King with Adel Taarabt, but the hosts were indebted to a brilliant Robinson save on the stretch from Farfan's drive to keep them at least in touching distance.
In fact, the visitors were the only team that looked like scoring in the closing stages and Farfan and then Timmy Simons wasted half-chances in the box.
Jamie O'Hara almost brought Tottenham a late reward, volleying Taarabt's deep cross narrowly wide from the angle, and Dimitar Berbatov forced a neat save with a drive, but it would have been ill-deserved after an uninspired display.
Tottenham: Robinson, Chimbonda, Woodgate, King (Taarabt 73), Gilberto (O'Hara 46), Lennon, Jenas (Huddlestone 64), Zokora, Malbranque, Berbatov, Keane.
Subs Not Used: Cerny, Lee, Tainio, Dawson.
Booked: Gilberto, Chimbonda, Berbatov.
PSV: Gomes, Kromkamp, Marcellis, Salcido, Alcides, Culina, Simons, Mendez, Farfan (Dzsudzsak 85), Koevermans (Lazovic 77), Afellay (Bakkal 90).
Subs Not Used: Roorda, Zonneveld, Rajkovic, Aissati.
Booked: Farfan.
Goals: Farfan 34.
Att: 33,259
Ref: Stephane Lannoy (France).
BBC Sport Player Rater man of the match: PSV's Jefferson Farfan 7.92 (on 90 minutes).
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