Callejon opened the scoring for Napoli after just five minutes and Mertens bagged a brace to make it 3-0 inside 25 minutes.
Marek Hamsik added a fourth early in the second-half and Callejon completed the Group D rout 13 minutes from time.
Morten Rasmussen struck as Midtjylland beat Legia Warsaw 1-0 in the other match in the group, in which the Poland side had Dominik Furman sent off.
Park Joo-ho headed a last-gasp winner as Borussia Dortmund came from behind to beat Krasnodar 2-1 in Group C.
Pavel Mamaev gave the Russian side an early lead at Signal Iduna Park, but Matthias Ginter levelled before the break and then set up Park's stoppage-time winner after Dortmund has dominated the second-half.
Elsewhere in the group, Qabala drew 0-0 with PAOK.
In Group A, Ajax twice came from behind to draw 2-2 with Rogic's Celtic in Amsterdam.
Nir Bitton and Mikael Lustig were on target for the Scotish champion while Viktor Fischer and Lasse Schone scored for the Dutch side.
Molde survived the late sending off of Mohamed Elyounoussi and a barrage of Fenerbahce chances to claim a 3-1 win in Istanbul.
Tommy Hoiland's penalty was cancelled out by Nani late in the first-half, but Molde hit back again after the break with goals from Elyounoussi and Martin Linnes.
Substitute Jussie scored a late equaliser as Bordeaux drew 1-1 in Group B with Liverpool, who had taken the lead through Adam Lallana.
While Sion beat Rubin Kazan 2-1 with a double from Moussa Konate.
Marseille began in Group F with a 3-0 win at Groningen with goals from Georges-Kevin N'Koudou, Lucas Ocampos and Romain Alessandrini while Braga won 1-0 at Slovan Liberec.
Rapid Vienna beat Villarreal 2-1 in Group E and Viktoria Plzen overcame Dinamo Minsk 2-0.
Meanwhile, Klaas-Jan Huntelaar maintained his impressive scoring record for Schalke in Europe with two goals in its 3-0 win at APOEL Nicosia in Group K. Joel Matip was also on target while the Cyprus side had Tomas De Vincenti sent off late on.
Asteras Tripolis and Sparta Prague played out a 1-1 draw in Greece as Pablo Mazza's early goal for the host was cancelled out by David Lafata.
New signing Son Heung-min scored a quickfire double to lead a Tottenham Hotspur fightback against Azerbaijan champion Qarabag at White Hart Lane.
Qarabag struck early through Richard Almeida's penalty but Son responded with two goals in as many minutes around the half-hour mark and Erik Lamela secured a 3-1 win in Group J, four minutes from time.
Group rival Monaco equalised in the 85th minute through Lacina Traore to snatch a 1-1 draw at Anderlecht. The Belgians had led since Guillaume Gillet scored in the 11th minute.
Last season's runner-up Dnipro scored an injury-time equaliser to snatch a 1-1 draw against Lazio in Group G.
Sergej Milinkovic-Savic's 34th-minute effort looked to have secured victory for the Italians in Ukraine but Yevhen Seleznyov had the final word with 94 minutes on the clock.
The other match in the group was also a draw as the clash between Saint-Etienne and Rosenborg ended 2-2.
Robert Beric and Tobias Mikkelsen traded early goals and Nolan Roux scored a late equaliser for the French side from the penalty spot after Jonas Svensson put Rosenborg ahead.
In Group L, Abubakar Oumaru struck twice as Partizan Belgrade claimed a hard-fought 3-2 win over 10-man AZ Alkmaar.
Jop van der Linden kept the Dutch, who had Guus Hupperts sent off, in contention until Andrija Zivkovic made the result certain in the 89th minute. Markus Henriksen scored an injury-time consolation.
There were also goals in the other Group L game as Athletic Bilbao beat Augsburg 3-1 with Aritz Aduriz on the scoresheet twice.
Goals from Birkir Bjarnason and Mohamed Elneny saw Basel come from behind to beat 10-man Fiorentina 2-1 in Group I.
Nikola Kalinic gave the Italians an early lead but the game changed after Gonzalo Rodriguez was dismissed.
Lech Poznan's clash with Belenenses ended goalless while, in Group H, Besiktas won 1-0 at Skenderbeu and Sporting Lisbon lost 3-1 at home to Lokomotiv Moscow.
