Valencia gained revenge for their 3-0 home defeat to Swansea by beating the Premier League side 1-0 in south Wales to confirm their place as Group A winners.
Dani Parejo struck in the 21st minute after the ball fell rather fortuitously to the former Liverpool man inside the area and he slipped it past Gerhard Tremmel.
Swansea remain favourites to take second place and require just a point when they travel to St Gallen next month.
Ludogorets Razgrad continued their impressive form in the competition as they saw off PSV Eindhoven 2-0 to finish top of Group B.
Roman Bezjak struck in either half to seal the win with PSV now needing to avoid defeat at home to Chornomorets Odesa to secure second spot.
Odesa moved level on seven points with PSV after beating Group B whipping boys Dinamo Zagreb 2-1 in Ukraine.
Fatos Beqiraj put the visitors ahead but Zagreb, who have just one point in the group, were beaten after two late headers courtesy of Oleksiy Antonov and Anatoli Didenko.
A late Martin Lanig goal gave Eintracht Frankfurt a 1-0 win over Europa League Group F rivals Bordeaux and secured progression into the knockout stages.
The German side have only lost once so far in the group and will go through as group winners after Maccabi Tel-Aviv could only draw 0-0 against APOEL in Nicosia.
The defeat means Bordeaux's poor European campaign will end following their final group game in Israel as they remain rooted to the bottom of the pool.
Zulte Waregem moved in to second place in Group D after winning 2-1 away against fellow hopefuls Wigan.
Defender Leon Barnett had put the English side ahead at the DW Stadium with a seventh-minute goal but Zulte fought back to move closer to sealing progression to the knockout phases.
Chelsea loanee Thorgan Hazard levelled after 37 minutes and the Beglian side secured the win when Bernard Malanda struck with just two minutes remaining.
Marco Meilinger scored in the first half to continue Red Bull Salzburg's 100 per cent record in Group C at the expense of Elfsborg.
The Austrian side had already picked up enough points to progress, as had their Group C rivals Esbjerg fB, who also won once more on Thursday evening.
Mick van Buren grabbed a brace for the Danish outfit as they beat Standard Liege 2-1, with Igor De Camargo scoring for the visitors.
Dnipro and Fiorentina continued their dominance of Group E with both sides already assured of their position in the final 32.
Fiorentina drew 0-0 at Pacos Ferreira whilst Dnipro won 4-1 at home to Pandurii Targu-Jiu.
Nikola Kalinic, Roman Zozulya, Yevgen Shakhov and Serhiy Kravchenko all found themselves on the scoresheet for the hosts, whilst Eric Pereira converted a consolation penalty for the Romanians.
Earlier this evening, Lazio were among a host of sides who secured progression in to the knockout stages as they eased to a 2-0 win away at Legia Warsaw.
Trabzonspor top Group J but Lazio will join them in the last 32 after a comfortable evening in Poland.
Brayan Perea put the Italians on their way in the 24th minute before Felipe Anderson doubled his team's lead before the hour mark.
Legia proved no threat for the Romans, who secured their third win in the competition.
Trabzonspor survived a fightback from Apollon Limassol to win 4-2 in their match in Turkey to remain at the head of the group, as Olcan Adin scored a hat-trick.
Adin opened the scoring with an early header with Soner Aydogdu doubling their lead before Adin grabbed his second.
Abraham Gneki Guie's header cut the deficit before Gaston Sangoy converted an 80th-minute penalty to make it 3-2.
Trabzonspor saw the game out, however, and Adin managed to complete his hat-trick with a late free-kick.
Lyon will also be in the draw for the round of 32 after beating Real Betis 1-0 at the Stade de Gerland.
Bafetimbi Gomis' 66th-minute strike settled the game and put Remi Garde's side through, although Betis are also into the next stage after the other group match between Rijeka and Vitoria Guimaraes ended goalless.
Anzhi Makhachkala put their domestic troubles behind them as they advanced with a 1-1 draw against FC Sheriff.
The Russians have yet to win a game in the Premier League but the point earned on Thursday night ensured they will finish second behind in Group K.
Ismail Isa had put the Moldovans ahead following a smart move but Alexandru Epureanu equalised from a corner to ensure Anzhi's qualification.
That draw meant Tottenham would top Group K no matter how they fared in Tromso.
After losing 6-0 at Manchester City in the Barclays Premier League on Sunday, Spurs responded well in Norway as Vlad Chiriches and Mousa Dembele both struck second-half goals to keep their 100 per cent Group K record in tact.
Rubin Kazan were prevented from sealing their position as Group D winners as Maribor scored a late equaliser to secure a 1-1 draw in their clash at the Central Stadium.
The draw is enough to confirm progression in to the knockout stages for Kurban Berdyev's side.
Bebras Natcho has put Rubin ahead before half-time but Dejan Mezga's late leveller earned Maribor a hard-fought point.
PAOK Salonika's hopes of topping Group L were given a boost as they emerged from Kazakhstan with a 2-0 win over Shakhtyor Karagandy.
Huub Stevens' side made the trip knowing qualification was in the can barring an unforeseen meltdown, but armed with the knowledge they needed a win for the purposes of their battle for top spot with AZ Alkmaar.
An unfortunate Aldid Dzidic own goal and a Stelios Kitsiou strike saw off a Shakyhtor side who have made little impression after initially being primed for the Champions League.
AZ also completed the job of seeing off Maccabi Haifa 2-0 to remain level with PAOK.
Nemanja Gudelj opened the scoring for the Dutch side, with Johann Berg Gudmundsson adding a second deep in to added time.
Genk saw off fellow Group G hopefuls Dynamo Kiev 3-1 to secure safe passage in to the knockout phase and leave the Ukrainian's sweating over their own progression.
Andriy Yarmolenko fired Kiev ahead in Belgium after just eight minutes but Jelle Vossen levelled from the penalty spot less than 10 minutes later.
The hosts then moved out of sight before half-time with Bennard Kumordzi and Benjamin De Ceulaer both scoring to secure the win.
Dynamo are now under threat from Rapid Vienna, who moved to within a point of second place following their 2-1 home win over FC Thun.
Terrence Boyd gave Vienna the lead before Berat Sadik levelled for the visitors after an hour.
Branko Boskovic restored Rapid's advantage less than three minutes later and they will now face a trip to Kiev in the final group game needing a win to advance to the next phase.
Kuban Krasnodar claimed their first win in Group A in style as they swept aside St Gallen 4-0.
Lorenzo Melgarejo was on target twice, opening the scoring in the third minute and getting the third 18 minutes from time.
Vladislav Ignatiev netted the second in the 55th minute and Charles Kabore rounded off the rout at the death as Kuban moved above their opponents into third place on five points.
Sevilla were held to a 1-1 draw at home to Estoril but that proved to be enough to see them through in Group H.
Kevin Gameiro's seventh-minute strike saw Sevilla take the lead but Miguel Ruben Fernandes scored in the last minute as Estoril secured their third point of the competition.
Freiburg won 2-1 away at Slovan Liberec to move level on six points with the Czech side.
Goals from Matthias Ginter and Arsenal loanee Francis Coquelin had put Freiburg in pole position and the German outfit survived a late Sergiy Rybalka goal to pick up three valuable points.