Yevhen Konoplyanka's late penalty earned Dnipro a 1-0 win over Tottenham in the first leg of their UEFA Europa League round of 32 tie.
Konoplyanka, a target of Liverpool in the January transfer window, slotted home an 81st-minute spot-kick after Jan Vertonghen was adjudged to have brought down Matheus inside the box, condemning Tottenham to their first European defeat of the season.
It was sweet revenge for Dnipro coach Juande Ramos, who delivered Tottenham's last trophy by winning the League Cup in 2008, only to be sacked the following season with the club bottom of the Premier League table.
The result leaves Tottenham with work to do in the second leg next week and it could have been an altogether different story for Tim Sherwood's men, who saw Roberto Soldado spurn a golden chance when he missed an open goal 10 minutes into the second period.
By the final whistle, though, Sherwood was thankful to depart with his side trailing by only the solitary goal as Roman Zozulya was denied by the frame of the goal in stoppage time.
Andros Townsend made his first start for Tottenham since mid-December after recovering from a hamstring injury, while 16-year-old Josh Onomah took his place on the bench for the first time.
On a dry and rutted surface, the visitors created the first half-opening of the game in the 13th minute after a minute's silence was observed in respect to those who lost their lives this week during the recent political unrest in Ukraine, Soldado seeing his near-post header blocked by Dnipro goalkeeper Denis Boyko.
Dnipro ought to have gone ahead 12 minutes later when Matheus was played clean through on goal, but Brad Friedel spread himself to block the Brazilian's effort low down to his left, before thwarting the striker again two minutes later when he tried his luck from 25 yards.
Ten minutes before the break, Ivan Strinic was booked for hauling down Paulinho on the edge of the area, with Tottenham arguing that he should have been sent off for denying a goalscoring opportunity. Townsend sent the resulting free-kick a yard wide.
Soldado wasted a glorious chance to break the deadlock in the 56th minute when, with the goal at his mercy, the Spaniard somehow cleared the crossbar from four yards after being picked out by Paulinho's ball across the box.
Sherwood introduced Christian Eriksen off the bench in place of Townsend in the 64th minute and the Denmark international almost made a telling contribution with his first touch, but his slotted finish beyond Boyko was ruled out for offside.
Friedel had to be alert three minutes later to parry Matheus' rasping effort from the edge of the box as the game became more stretched.
Soldado saw a volley blocked before Friedel was involved again, rushing from his line to deny Giuliano after the Brazilian had jinked his way through the Tottenham defence.
The deadlock was eventually broken when Vertonghen brought down Matheus and Konoplyanka coolly tucked home the penalty in off the left-hand post to give Dnipro a crucial first-leg advantage.
Tottenham pushed hard for an equaliser as Paulinho forced a ricochet that struck the base of the post before substitute Harry Kane failed to get a telling connection with the goal at his mercy.
It could have been so much worse for Tottenham, though, as Zozulya sent a header against the post in stoppage time.
|Coach: Juande Ramos|
for Giuliano 77'
for Matheus Nascimento 90'
|Griezmann at the double in Atletico win|
|Japan v South Korea: Halilhodzic calls for ´pride´|
|Mourinho enjoying improved relationship with Abramovich|
|Gradel agrees Bournemouth return|
|Inter switch an ´easy decision´ for Miranda|
|Bojan eyes early comeback|
|Vitesse hopeful over Solanke loan deal|
|Pedro will decide his own future - Luis Enrique|
|Iniesta handed Barcelona armband|
|Kukesi punished after Europa League abandonment|
|Leno hints at Leverkusen exit|
|Benitez explains Ronaldo absence|
|Pochettino backs Kane to be among world´s best|
|Messi not ruled out of Mexico friendly - Martino|
|China v North Korea: Kim´s side look for another win|
|River Plate v Tigres UANL: Copa Libertadores final evenly poised|
|Torres: I´d give my life to win La Liga with Atletico|
|Real target Ceballos focused on Betis - Mel|
|Platini can lead FIFA change - Fernandez|
|Mel: Betis won´t be signing Osvaldo|
|Ferrero defends Samp boss Zenga|
|Pochettino expects Spurs improvement|
|Bale ideal for United - Robson|
|Ferdinand: Di Maria will regret United failure|
|Benitez pleased with goalkeepers as De Gea transfer saga continues|
|Guardiola tips fit Schweinsteiger to shine|
|Confident Oxlade-Chamberlain hits back at Keane|
|Ferdinand: Stones would be ´a lunatic´ to join Chelsea|
|Qarabag v Celtic: Gordon wants positivity from Scottish champions|
|Higuain rejects extension from Napoli|
|Zamora returns to Brighton|
|West Ham can cope without Valencia - Gold|
|Wickham loses on Palace debut|
|Guardiola: No problem with Matthaus and Effenberg comments|
|Cartabia excited by Deportivo loan|
|Lyon confirm Rafael deal|
|Hysaj agrees deal to follow Sarri to Napoli|
|Rafael says his goodbyes to Manchester United|
|Dos Santos ready to get going with Galaxy|
|Pochettino rejects Soldado exit talk|
|Metatarsal misery for Mulumbu|
|Benitez: Benzema and Bale going nowhere|
|Mihajlovic: Ibrahimovic would make Milan title contenders|
|Hughes not taking any risks with Bojan|
|Guardiola relishing Audi Cup test|
|Di Maria ´taking a step up´ - Silva|
|Leicester bring in defender Benalouane|
|Deulofeu doubtful for Premier League opener|
|West Ham striker Valencia out for three months|
|UEFA: Qarabag-Celtic to go ahead|
|Palace seal Wickham swoop|
|Ronaldo and Benzema to miss Audi Cup|
|Marotta: Juventus could lose Pogba|
|Kante completes Leicester switch|
|Khedira ruled out for two months|
|FA accepts Mourinho criticism of Wembley surface|
|Robben rubbishes injury talk|
|Marchisio expects Milan title challenge|
|Rafael set for Lyon move|
|Celtic ´seeking reassurances´ over Qarabag pitch|
|Wenger beating Mourinho does not affect Chelsea - Zouma|
|Rooney moved by Everton welcome|
|Mancini not worried by lack of Inter goals|
|Coloccini wants to finish career at Newcastle - McClaren|
|Ramsey: Pressure to win trophies is nothing new|
|Terry: Wembley defeat could be a ´blessing in disguise´|
|Blatter not running for IOC re-election|
|Bendtner: Wolfsburg can challenge Bayern for Bundesliga honours|
|Liverpool relishing Britannia return, says Henderson|
|Everton big enough to keep Stones - Martinez|
|MLS Review: Fire stun Dallas as goals dry up|
|New Atletico signings excite Raul Garcia|
|Cahill expects Arsenal title challenge|
|Jovetic happy with Inter debut|
|Luis Enrique: Barca defence must improve|
|Yanev calls for calm after ugly scenes in friendly|
|Coppa Italia Review: Cittadella romp to victory, Brescia rely on penalties|
|Arsenal have learned how to play against big teams - Ramsey|
|Shawcross to visit specialist over back woe|
|Fiorentina 2 Barcelona 1: Bernardeschi double sends Barca to another defeat|
|Mancini hints at Melo interest|
|Rodgers hails ´incredible´ Benteke strike|
|Galatasary 1 Inter 0: Sneijder sinks former club|
|Wenger defends Arsenal approach|
|Wembley loss has no bearing on new season - Terry|
|Porto cruise to friendly win over Stoke|
|Mourinho denies Wenger ´snub´ suggestions|
|Arsenal abandoned their philosophy to win Community Shield - Mourinho|
|Mourinho throws Community Shield medal into Wembley crowd|
|Swindon Town 1 Liverpool 2: Benteke nets stunner on debut|
|Scottish Premiership Review: Hearts win thriller on top-flight return|
|Ujah at the double as Bremen beat West Ham|
|Mourinho: We were the better team|
|Wenger hails defensive solidity|
|Rooney returns as Villarreal spoil Ferguson´s party|
|Rodriguez stunner earns Southampton draw as Caulker makes debut|
|Arsenal 1 Chelsea 0: Case of 14th time lucky for Wenger against Mourinho|
|Taechaubol announces Milan agreement|
|Jojic fires Cologne to latest victory|
|China 0 South Korea 2: Kim and Lee seal victory|
|Origi getting up to speed|
|Costa a doubt for start of season - Mourinho|
|North Korea 2 Japan 1: Halilhodzic´s men spurn lead|
|Allam brands FA ´amateurs´ as name-change row rumbles on|
|Fournier ´worried´ by Lyon pre-season|
|Swansea still working on Michu exit - Monk|
|Neuer furious at Bayern Supercup defeat|
|Wenger: Ozil signing not a mistake|
|UEFA Champions League Preview: Shakhtar ready for Fenerbahce decider|
|Lampard targets MLS play-offs for City|
|MLS Review: Goals galore as DC United win 10-goal thriller|
|Ronaldinho returns and helps Fluminense to win|
|Keane: United won´t overtake Chelsea|
|Casillas has the ´enthusiasm of a 20-year-old´ - Lopetegui|
|Blanc hopeful over Ibrahimovic knee injury|
|Guardiola laments late goal in Supercup defeat|
|Tuchel plans to keep Bender|
|Hecking happy with Wolfsburg discipline after Supercup win|
|Arsenal players too interested in selfies and six-packs - Keane|
|Confusion over Ibrahimovic´s PSG future|