The Spanish attacker put the visitors ahead and his Colombian teammate added the second, ensuring Andre Ayew's late strike was a consolation only.
Napoli strengthened its hopes of qualification for the Champions League knockout stages with a 2-1 win at Marseille on Tuesday.
The Italian side headed into the game looking to bounce back from its 2-0 defeat to Arsenal in the previous round of Group F.
Marseille was without a point following losses against the Gunners and Borussia Dortmund, and its hopes of progression were dealt a further blow as Napoli cruised to a comfortable victory.
Former Real Madrid winger Jose Callejon and Colombian attacker Duvan Zapata put Napoli command, before Andre Ayew pulled one back for Marseille to set up a tense finish.
Napoli is tied for the group lead on six points with Arsenal and Dortmund following the German side's 2-1 win at the Emirates Stadium, but Marseille is well adrift at the bottom.
Dimitri Payet returned for Marseille after serving a domestic suspension over the weekend, while defender Souleymane Diawara and midfielder Benoit Cheyrou also came into the side.
The inclusion of striker Gonzalo Higuain was one of four changes made by Napoli coach Rafa Benitez, who also restored winger Dries Mertens to the starting XI in place of Lorenzo Insigne following Friday's Serie A defeat to Roma.
Marseille keeper Steve Mandanda was tested early when he was forced into a fine diving save to prevent winger Mertens from finding the net with a free kick after just two minutes.
However, Napoli controlled much of the early stages. Although midfielder Cheyrou went close for Marseille, it should have taken the lead in the 13th minute when defender Pablo Armero fired wide from close range.
The hosts frustrated Benitez’s side for long periods, but they were almost caught out on the counterattack when Higuain inexplicably fired wide with only Mandanda to beat.
But three minutes before the break, Napoli did deservedly go ahead as Callejon displayed great control to bring down Higuain's wonderful ball over the top before cutting inside Rod Fanni and firing a half-volley beyond Mandanda.
Marseille made a quick start to the second half, and nearly drew level seven minutes after the break, only for Payet to head over the bar.
Elie Baup's side dictated the play for large periods as it looked to craft an equalizer, but its lack of quality in front of goal was summed up when Ayew failed to connect with a right-wing cross from Payet. And its hopes were all but ended after 66 minutes when substitute Zapata curled a glorious right-footed effort into the top corner after latching onto a deft flick-on from Mertens.
Marseille labored to find a way back into the game in the closing stages. Although Ayew found the net with a superb low volley four minutes from time, the 1992-93 European champions could not complete a late comeback and now face an uphill struggle to avoid finishing at the bottom of the group.