The Argentine scored his second goal with 15 minutes remaining to settle a superb contest at the San Paolo stadium.
Florian Thauvin had levelled for the visitors on 64 minutes after two brilliantly-taken goals from Napoli's Gokhan Inler and Higuain in as many first-half minutes had cancelled out Andre Ayew's headed opener for the French side.
The win moved Rafael Benitez's side into second place in the group on nine points, level with leaders Arsenal who won at Borussia Dortmund. Marseille's fourth straight defeat means they will finish bottom of the group.
The win could prove crucial for Napoli as they now travel to Dortmund for their next match in three weeks with a three-point cushion over the Germans, having beaten them 2-1 in their opening match.
Ayew's 10th-minute goal came as Marseille surprised nervy Napoli with swift, confident passing. Napoli, though, equalised 12 minutes later after Federico Fernandez's header was saved by Steve Mandanda and Swiss international Inler pounced on a poor clearance to bring down the ball with his chest and score with an arching shot.
With Marseille reeling, Higuain quickly put the hosts in the lead with a superb volleyed finish, racing on to Goran Pandev's deflected knockdown to shoot low and hard past Mandanda.
Thauvin silenced the Napoli fans when he nipped past a dozing Pablo Amero to collect substitute Dimitri Payet's cross and volleyed past goalkeeper Pepe Reina.
Eleven minutes later, Dries Mertens sprang Marseille's offside trap and crossed low to Higuain, who made no mistake from close range and sealed a huge victory for Napoli.
- Sports & Recreation
- Florian Thauvin
- Andre Ayew
- Rafael Benitez
- Borussia Dortmund