But while it was a disappointing day for Eddie Howe's side, who take on Manchester United in the Carabao Cup final at Wembley next weekend, they can at least take heart from the way they competed against last season's top-flight runners-up with a player less for more than an hour.
Darwin Núñez and Cody Gakpo had already put Liverpool two goals ahead before Nick Pope was sent off, but United refused to cave in and hit the woodwork, as well as creating other opportunities - including a great chance for Callum Wilson with just over ten minutes left.
Sir Bobby Robson and Christian Atsu were both remembered before kick-off; Sir Bobby with a poignant flag display on what would have been his 90th birthday and Atsu, who tragically lost his life in Turkey's devastating earthquakes, with a minute's silence which spontaneously became applause.
And seemingly channelling the emotion among the supporters, United started well, almost taking the lead in the fourth minute when Allan Saint-Maximin found Miguel Almirón, whose shot was smothered Alisson, off his line in a flash.
Howe's men continued to be on the front foot but were stunned in the tenth minute, when Trent Alexander-Arnold lofted the ball towards Núñez, who beat the offside trap and smashed beyond Pope.
Newcastle tried to respond immediately, with Saint-Maximin having an effort blocked by Virgil van Dijk, but found themselves two down in the 17th minute as Mohamed Salah's clipped pass was slid home by Gakpo.
And things went from bad to worse for the Magpies five minutes later. Alisson's quick kick sent Salah scampering away but Pope came to meet the ball with a diving header outside his area. However the Newcastle netminder failed to connect, then handled the ball as he tried to recover and was shown a straight red card by referee Anthony Taylor.
Not only were United now down to ten men, but Pope will miss the Carabao Cup final. Martin Dúbravka - who is cup-tied for next Sunday's game at Wembley - was brought on, with the unfortunate Elliot Anderson sacrificed in his first Premier League start.
With his first touch, Dúbravka saved Gakpo's header from the resulting free kick, taken by Alexander-Arnold, and despite their numerical disadvantage Newcastle were the better side for the rest of the half.
In the 31st minute, Saint-Maximin superbly made space for a strike from the right-hand side of the box which was brilliantly kept out by Alisson, then Trippier's corner was met by the head of Fabian Schär but blocked by a Liverpool defender.
From another flag-kick, Dan Burn's header at the far post was flicked towards goal by Joelinton but fielded by Alisson.
Burn crashed a header against the bar in the 41st minute, from another corner taken by Trippier, then in first-half stoppage time Almirón shot side.
And United kept battling in the second period too, with Isak coming close with a shot on the turn after good work from Saint-Maximin and Schär nodding wide in the 55th minute from another set-piece.
Dúbravka made a good save from Núñez, then a more routine stop from substitute Harvey Elliott in the 68th minute, and he was called into action once more in the 81st minute to gather an effort from Salah.
But it was Alisson who made a crucial intervention moments later. Substitute Anthony Gordon embarked upon a strong run before sliding in Wilson, but he was denied by the Brazilian, who ensured there would be no grandstand finale despite the Magpies' brave efforts.
Diogo Jota sent two late headers wide, then had an effort cleared off the line in stoppage time but a third goal would have been harsh on United, who were applauded off the pitch despite the defeat and will now look to bounce back by lifting a first domestic trophy since 1955 in eight days' time.
