Dries Mertens and Fernando Llorente scored late goals as Napoli defeated holders Liverpool 2-0 in Tuesday's opening round of Champions League group stage matches.
Mertens converted a penalty on 82 minutes and Llorente added a second in stoppage time as Napoli gained a measure of revenge for last season's 1-0 loss at Anfield that denied the Italians a spot in the knockout rounds.
Jurgen Klopp's side are the first reigning European champions to lose their opening game of the following campaign since AC Milan in 1994.
Both Liverpool, who sit top of the Premier League after five straight wins, and Napoli remain favourites to progress from Group E despite Salzburg's thrilling 6-2 win over Genk.
Llorente joined Napoli this season after playing his last game for former club Tottenham in the Champions League final defeat by Liverpool in Madrid in June.
He came on as a substitute and pounced on a rare Virgil van Dijk blunder after Mertens had opened the scoring from the spot to pandemonium among the crowd at the Stadio San Paolo.
Liverpool also lost their group-stage match in Naples last season before going on to lift a sixth European Cup.
Both teams could thank their goalkeepers for keeping the scoreline goalless for so long.
Adrian made his Champions League debut in the Liverpool goal with Alisson Becker out injured, pulling off an impressive save from a Mertens volley just after the break.
At the other end, Napoli goalkeeper Alex Meret was also at full stretch, denying Mohamed Salah with his fingertips on 65 minutes.
Napoli's Senegalese defender Kalidou Koulibaly had his hands full with Salah who had threatened to break the deadlock throughout the first half.
Carlo Ancelotti's side piled on the pressure early on, with Adrian pulling off a double save in the seventh minute from Fabian Ruiz before Hirving Lozano headed into the net from an offside position.
Liverpool forward Sadio Mane dispossessed Insigne, forcing Meret into a save on 20 minutes with James Milner firing over.
Salah finally managed to break free of the towering presence of Koulibaly, with Mane combining with Firmino who fired over.
Firmino -- making his 200th appearance for Liverpool -- missed a chance to put the visitors ahead before the break with his header flashing wide.
The breakthrough came eight minutes from time after Jose Callejon went down easily in the box under pressure from Andy Robertson, with Mertens slotting in the penalty after a VAR review.
And Llorente pounced on Van Dijk's loose pass to claim his first Napoli goal, sealing a famous win for the hosts.