A further 10 sides, including Trabzonspor and Olympique Lyonnais, confirmed their qualification from the group stage as Fiorentina and Betis slipped up
The Biancocelesti secured a 2-0 win away to Legia Warsaw courtesy of goals from Brayan Perea and Felipe Anderson to confirm their qualification along with Group J leaders Trabzonspor, who beat Apollon 4-2.
Sevilla, meanwhile, ensured their place in the next round despite being held to a 1-1 draw by Estoril, after a last-gasp goal from Ruben Fernandes cancelled out Kevin Gameiro's early opener.
The Liga outfit's progress was assured after Freiburg won 2-1 away to Slovan Liberec, with one of these two sides set to join Sevilla in progressing from Group F.
A much-changed Fiorentina side lost their 100 per cent record after they were held to a goalless draw with Pacos Ferreira, meaning they face a deciding encounter with Dnipro Dnipropetrovsk on matchday six to determine who wins Group E after the Ukrainians thrashed Pandurii 4-1.
Elsewhere, Bafetimbi Gomis struck in the closing minutes to seal Olympique Lyonnais' place in the next round with a 1-0 win over Real Betis, with the Andalusians joining les Gones in the knockouts after Victoria Guimaraes were held by HNK Rijeka.
Goals from Nemanja Gudelj and Johann Gudmundsson saw AZ Alkmaar seal their place in the last 32 and put Maccabi Haifa out of the tournament, with PAOK's win over Shakhter Karagandy also sending them through from Group L.
Anzhi Makhachkala's draw with Sheriff means they will follow group winners Tottenham into the next round, while Kuban Krasnodar thrashed Swiss side St Gallen 4-0 to ensure they can yet overhaul Swansea City in Group A, after the Welsh side lost to Valencia.
Genk came from a goal down to beat Dinamo Kiev 3-1 thanks to Jelle Vossen, Bennard Kumordzi and substitute Benjamin De Ceulaer, while Rapid Vienna's 2-1 win over Thun means they can yet join the Belgians in the next round.
In Group C, Salzburg and Esbjerg pulled further away at the summit after wins over Elfsborg and Standard Liege, while PSV's 2-0 defeat to Group B winners Ludogorets means their final clash with Chornomorets Odessa will decide who goes through to the next round.
Rubin Kazan's draw with Maribor was enough to win their group, while Eintracht Frankfurt's win away to Bordeaux put them top of Group F following Maccabi Tel-Aviv's goalless draw with Apoel.