The Magpies were cruelly beaten 2-1 by AC Milan at St. James' Park despite taking the lead, and now their European dream is over.
It was all going so well for Eddie Howe and co. as they sat top of Group F after two games, but back-to-back defeats against Borussia Dortmund and a highly controversial draw at Paris Saint-Germain left it all to do on Wednesday night.
Newcastle needed to beat Milan on their home turf and hope that Dortmund beat or drew against PSG to reach the last 16, and an excellent strike from Joelinton put them in control.
Christian Pulisic's equaliser proved to be a hammer blow though and the Milan turnaround was completed by Samuel Chukwueze late on, with the other Group F clash ending in a 1-1 draw.
Newcastle are therefore out of Europe entirely having finished bottom of the group and Howe cut a sombre figure at full-time, but displayed pride in his side not straying away from their values of being entertainners despite defeat.
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In his post-match press conference, he said: "We'll always try and be proactive rather than reactive. I'd like to think that's the Newcastle Way."
He also insisted there was nothing more his players could do on what was a disappointing night, one that could lead fans to rue mistakes in past matches:.
Howe added: "I think we gave everything to the match," he told TNT Sports.
"I don't think I could ask anymore of the players, commitment, effort, physical exertion. Unfortunately for us, it wasn't to be today, I thought there were some really good bits in our performance.
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"I thought we were dominant at times, we probably needed the second goal. We didn't defend the two goals well enough."
PSG's late equaliser last month, which came after Tino Livramento was contentiously adjudged to have handled in the box, did nothing but add to the pressure on Newcastle's shoulders.
There will be many that believe it played a huge role in the Magpies' exit from Europe, but Howe is not one to dwell on past decisions, saying: "I think it would be foolish of me to look back at that moment now and start bringing up old stuff.
"We had the opportunity tonight to do what we needed to do, we didn't take it, but it's not through a lack of effort. As we've said many times we've got a very stretched squad.
"Those players are going again and again and I couldn't be prouder of what they've given me physically, mentally and I do think we've left everything on the pitch.
"I don't think we can have any regrets but of course we'll learn form it and try and absorb all the things that we need to take into our Premier League form."
Securing a top four finish in the Premier League is now the aim for Newcastle, who are also still in the Carabao Cup and yet to play in the FA Cup.
No European football for the rest pf the season will undoubtedly be a real shame for them, but Rio Ferdinand believes it will help their extensive list of injured players return sooner rather than later.
He told TNT Sports: "Eddie Howe and the players can't say this but I'm guaranteeing you now, they'll be delighted I think to not go into the Europa League.
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"The amount of injuries they've got, Kieran Tripper just limped past us here, talking about the amount of injuries that they've got and a few of them are medium to long-term.
"It makes it very difficult to be battling on many fronts in different competitions when your squad is so threadbare. They have to get these players back fit, and more and more games would make it more unlikely for those players to come back fit."