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'
|Kovacic to miss Euro 2016 qualifier|
|Costa Rica 0 Paraguay 0: Dour draw marks Diaz debut|
|Reid ruled out of South Korea friendly|
|Deschamps talks up France despite defeat|
|Rooney chasing England goalscoring record|
|Brazil ´superior´ admit French veterans|
|Reeves sidelined for Finland clash|
|Confidence critical for rampaging Brazil - Dunga|
|France 1 Brazil 3: Dunga´s men maintain winning run|
|Chile 0 Iran 2: Nekounam and Amiri down Copa America hosts|
|Premier League to share over £1bn from record TV deal|
|Morocco v Uruguay: Last chance to impress Tabarez for Copa champions|
|Iran 2-0 Chile: Nekounam and Amiri down Copa America hosts|
|Ivanovic braced for Ronaldo test|
|Bahrain 0 Colombia 6: Falcao stars in comfortable victory|
|Jones to Bournemouth leads loan deadline day moves in Championship|
|Bahrain 0-6 Colombia: Falcao stars in resounding victory|
|Malmo fined for poor pitch by UEFA|
|League Two Preview: Hartlepool aim to continue great escape, leaders Burton host Stevenage|
|France 1-3 Brazil: Neymar on target as Selecao triumph in Paris|
|Bulgaria v Italy: Verratti vows to be Azzurri´s midfield general|
|Kane primed for full England debut|
|Kone receives positive news over knee injury|
|Terry pens new Chelsea deal|
|PSG tie down Marquinhos|
|De Gea stamp was accidental - Skrtel|
|Villa hopeful over Xavi reunion|
|El Salvador v Argentina: Messi set for Roca reunion|
|Ghana v Senegal: Grant´s side looking to rebuild after AFCON disappointment|
|Ferdinand to serve extended touchline ban|
|League One Preview: Duo aiming to inspire Notts County revival, Alexander back at Preston|
|Hodgson keeps an eye on Sterling and Milner|
|Filipe Luis cools talk of Atleti return|
|West Brom to wear retro kit for Leicester clash|
|Netherlands v Turkey: Sneijder unconcerned by key absentees|
|Del Bosque wary of Ukraine threat|
|Israel v Wales: Pivotal fixture for both sides in chase for Euro dream|
|Bosnich backs Villa to beat drop|
|Walcott denies Wenger ´bust-up´|
|Hart: Aguero more difficult to face than Messi|
|Williams: I can´t see myself playing for anyone else|
|Coutinho eager to add more goals to his game|
|Khedira confirms Real exit|
|Messi attends NBA match with Argentina squad|
|United will qualify for Champions League - Bosnich|
|Mexico v Ecuador: Hernandez desperate to play|
|Podolski plays down Germany cameo|
|Bendtner: I could have scored four|
|Leverock family adds to World Cup exploits for Bermuda|
|Pele: ´Impossible´ for Neymar to replace me|
|MLS Preview: New England hoping to end drought|
|A-League Preview: Phoenix without stars for Sydney showdown|
|Klinsmann laments late collapse|
|Premier League clubs post first pre-tax profit for 15 years|
|Vokes relishing chance to link up with Bale|
|Dunga encourages Brazil to entertain|
|Dyke: FA to discuss Hodgson extension|
|Janko eyes history with Austria|
|Wilson urges Begovic to stay put|
|Strachan: Scotland have work to do|
|Sky´s the limit for Australia - Postecoglou|
|Low unhappy with below-par Germany|
|Scotland 1 Northern Ireland 0: Berra´s header settles dour contest|
|Germany 2 Australia 2: Substitute Podolski salvages draw|
|Denmark 3 United States 2: Bendtner hat-trick rescues Danes|
|Scotland 1-0 Northern Ireland: Berra the unlikely hero for hosts|
|Gobbi: Players will ´pay the price´ to keep Parma afloat|
|Rose withdraws from England squad|
|Germany 2-2 Australia: Podolski rescues draw for World champions|
|Denmark 3-2 USA: Bendtner hat-trick wins it for the Danes|
|Nigeria 0 Uganda 1: Late winner sours Enyeama landmark|
|Swaziland 1 South Africa 3: Bafana Bafana back to winning ways|
|Camp Nou to host Copa del Rey final|
|Labadie charged with violent conduct after biting claims|
|Bender keen to rekindle Bayern rivalry|
|Swansea eager to tie down Taylor|
|Varane learning from Real troubles|
|Forster ruled out for rest of season|
|Inter full-back Dodo has successful surgery|
|Verratti focused on future at PSG|
|Minnesota awarded MLS expansion team|
|Ibrahimovic slams ´b******t´ PSG exit rumours|
|Gibson withdraws from Ireland squad|
|Ozil convinced he can win Ballon d’Or|
|Costa: I take a beating from Premier League defenders|
|Canada v Guatemala: Floro seeks to develop winning mentality|
|Vermaelen returns to Barcelona training|
|Euro 2016 Qualifying Preview: Spain face big Ukraine test, Germany visit Georgia|
|Spain v Ukraine: Morata set for first competitive start|
|England v Lithuania: Hart urges Kane not to leave U21s behind|
|Monchengladbach snap up Hannover skipper Stindl|
|Khedira gives strong hint of Real exit|
|Skrtel banned for three matches|
|Brisbane Roar 1 Western Sydney Wanderers 4: Champions´ title defence in tatters|
|Sampdoria swoop for Ajax captain Moisander|
|Barnes: Sterling not ready for big-money move|
|Ferdinand: Ramsey appointment a gamble|
|Ideye hopeful of facing QPR|
|Lampard eyes MLS showdown with Gerrard|
|Ronaldo could face suspension over Clasico celebration|
|Hodgson expects more withdrawals|
|Schalke fans overwhelm Farfan after injury lay-off|
|Swedish third-tier club Dalkurd avoid Germanwings flight|
|Japan v Tunisia: Halilhodzic takes charge of hosts for first time|
|Schweinsteiger brushes aside captaincy pressure|
|Barzagli supports Conte call-ups|
|South Korea v Uzbekistan: Stielike searching for improvement|
|France wary of more balanced Brazil|