Record-signing Erik Lamela scored his first goal for Tottenham, and Jermain Defoe converted the winning penalty kick in a 2-1 victory over Sheriff Tiraspol in Group K.
U.S. star Brad Friedel was in goal for Tottenham.
In Romania, Fiorentina won by the same score at Pandurii Targu Jiu after Matos Ryder and Borja Valero scored for the Group E leader, while second-place Dnipro of Ukraine advanced by beating Pacos Ferreira 2-0.
Two teams also are through already from Group C, with leader Red Bull Salzburg winning 3-1 at Standard Liege, and Esbjerg edging Elfsborg 1-0.
Valencia went to the top of Group A with a 3-2 win over St. Gallen, and will advance to the last 32 along with Russian side Rubin Kazan, Dnipro of Ukraine, and Ludogorets of Bulgaria.
At White Hart Lane, Lamela finally made his mark more than two months after joining from Roma for up to $47 million.
The 21-year-old Lamela has been used sparingly by Andre Villas-Boas and is yet to start an English Premier League game for Spurs but he showed his attacking prowess against the Moldovan champions.
Lamela knocked home the opener from close range on the hour before being tripped shortly afterward in the penalty area, Defoe scored from the penalty spot in the 67th. Although Ismail Isa struck a late consolation, there was no comeback to deny Tottenham a fourth straight Group K win.
''Lamela was unbelievable tonight, good on the ball, strong,'' Defoe said. ''Sometimes it is difficult coming to a new club at such a young age.''
Tottenham will have to wait to confirm its status as group winner after second-place Anzhi Makhachkala beat Tromso 1-0 in Norway.
In Group A, late goals from Pablo Piatti and Sergio Canales helped Valencia come from behind to beat 10-man St. Gallen 3-2 in Switzerland and replace Swansea as leader after the Welsh side drew at Kuban Krasnodar.
Bulgaria's Ludogorets lost its perfect record and conceded its first goal in Group B, but a 1-1 home draw with Chornomorets was enough for it to qualify. Second-place PSV Eindhoven closed the gap at the top to three points with a 2-0 home win over Dinamo Zagreb.
Rubin Kazan has all but done enough in Group D after beating English second-tier side Wigan 1-0 in Russia to go five points clear. Belgian side Zulte-Waregem gave itself hope of snatching second place with a 1-0 win over Maribor in Slovenia.
In Group F, leader Eintracht Frankfurt surprisingly lost 4-2 in Israel to Maccabi Tel Aviv, which is two points behind in second. APOEL Nicosia moved off the bottom with a 2-1 win over Bordeaux.
Trabzonspor all but booked its passage from Group J by winning 2-0 win at bottom-placed Legia Warsaw. Lazio remain hot on the leader's heels after a 2-1 win over Apollon in Rome.
In Group I, Chuli scored in stoppage time for Real Betis to clinch a 1-0 victory over Vitoria Guimaraes in Portugal, lifting the Spanish side to top spot as former leader Lyon was held to 1-1 at Rijeka.
Betis' city rival Sevilla continued to edge toward qualification from Group H after a 1-1 home draw against Slovan Liberec.
Also in Group H, Freiburg's Karim Guede and Nicolas Hofler were sent off in the final four minutes but the team managed to hang on for 0-0 with Estoril in Portugal.
Dynamo Kiev also shrugged off a numerical disadvantage as an own goal from Lukas Schenkel and a free kick from Andriy Yarmolenko clinched a 2-0 victory at Thun in Group G, despite the 17th-minute dismissal of Dieumerci Mbokani.
Genk's lead in the group was cut to a single point after a 2-2 draw at Rapid Vienna.
American forward Terrence Boyd scored in the 40th minute and again in first-half stoppage time for Rapid Vienna.
AZ Alkmaar went top of Group L with a 1-0 win over Shakhter Karagandy, replacing PAOK, which drew 0-0 with Maccabi Haifa.
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- Erik Lamela
- Jermain Defoe