The Reds were hoping to improve on the result at Stadio San Paolo last year as they took on Carlo Ancelotti's side for the second year running in Group E.
Despite a significantly better performance that saw them dominate in the second-half, it was the same outcome for Jurgen Klopp's side as they went back home without a point.
With a little under ten minutes to go, Andy Robertson was adjudged to have brought down Jose Callejon in the penalty area, despite VAR replays showing minimal contact between the duo. The penalty stood, to much dismay, with Dries Mertens stepping up and converting from the spot.
The home side then doubled their lead in extra-time to wrap up the game as Reds defender Virgil van Dijk made an uncharacteristic error to allow Fernando Llorente the chance to finish home past Adrian.
It was Liverpool's first defeat of the 2019/20 campaign and not the way Klopp would have liked his side to start their European campaign. However, there is no need for any soul-searching just yet.
Barring the two mistakes, the Reds showed a professional display away from home and they looked much improved from last year's dismal performance, despite the result not reflecting their efforts.
Klopp's side now sit in third in Group E, with RB Salzburg defeating Genk 6-2 in the other Group E fixture on the night. Liverpool are back in action this Sunday as they take on Chelsea at Stamford Bridge in the Premier League.
Slide through our gallery below for all the best snaps from Naples.