Atsu had previously beaten Tottenham Hotspur - controlled by former Magpies midfielder Moussa Sissoko - to progress into the last eight but he could not go a step further against one of the tournament favourites.
Perfect start
Atsu got off to the perfect start against Alexander-Arnold, with Allan Saint-Maximin putting the finish touch to a rapid counter attack at a virtual Anfield.
But the Reds’ full-back responded immediately, equalising with nine minutes on the clock before forcing Martin Dúbravka into a string of saves.
Alexander-Arnold then went in front just before half-time - former United midfielder Gini Wijnaldum finding the net - before Liverpool hit the woodwork twice from a flurry of attacks either side of the break.
Atsu almost found an equaliser after forcing the Liverpool goalkeeper into a fine block on the hour, but the hosts attacked again and quickly stretched their lead.
With Alexander-Arnold using the same tactic in the final third - getting the ball to the byline and cutting a low cross to the back-post - he created a simple finish for Mo Salah to establish what would become an unassailable lead.
The game was put to bed in the closing stages as Roberto Firmino scored Liverpool’s fourth with a fine finish, before Atsu came close to the tournament’s first goal direct from a free-kick, only for Joelinton’s superb effort to came back off the crossbar with the goalkeeper stranded.
Watch the Grand Final
The ePremier League Invitational Grand Final - including the semi-final stage and tournament final - will be LIVE on Sky Sports Main Event (UK) and Sky Sports and Premier League online channels from 3pm (BST) on Saturday 25th April.
About the ePL Invitational
The ePL Invitational tournament is operated by esports tournament organisers Gfinity.
For more information, please visit premierleague.com/epl-invitational.