Napoli had no problems beating FC Zurich 2-0 at home to advance 5-1 on aggregate, while Inter Milan also strolled through with a 4-0 home win over Rapid Vienna which completed a 5-0 dismissal.
Goals by Simone Verdi and Adam Ounas sent Napoli on their way and Inter followed in their footsteps as Matias Vecino, Andrea Ranocchia, Ivan Perisic and Matteo Politano made light work of their return leg against Rapid.
Eintracht Frankfurt beat Shakhtar Donetsk 4-1 to earn a 6-3 overall victory.
Following a 2-2 draw in Ukraine, Eintracht thumped Shakhtar in an action-packed encounter with Sebastian Haller and Luka Jovic putting the German side in the driving seat before Junior Moraes pulled one back for the visitors.
Salzburg were the other big winners as their 4-0 home rout of Club Bruges gave the Austrian side a 5-2 aggregate win, while two goals from Iran forward Sardar Azmoun handed Zenit St Petersburg a 3-2 overall success against Fenerbahce.
Croatian champions Dinamo Zagreb thrashed Viktora Plzen 3-0 for a 4-2 aggregate win over the Czechs.
Bayer Leverkusen were the surprise casualties after a 1-1 home draw with Krasnodar sent the Russian side through on away goals and Real Betis were beaten by Rennes 6-4 on aggregate following a 3-1 home defeat by the French side.
Slavia Prague stunned Belgians Genk 4-1 away after a goalless first leg and Dynamo Kiev edged Olympiacos 3-2 on aggregate thanks to a 1-0 home win in the return fixture.
A 0-0 home draw with Galatasaray was enough to see former European Cup winners Benfica through after their 2-1 away win a fortnight ago.