Milan were barely in the game in the first half, with a wayward Rafael Leao shot their only moment of excitement.
But Pulisic’s goal - a close-range finish after a low cross bobbled around Newcastle’s area - came out of nowhere and turned the encounter on its head.
Mike Maignan then produced a stunning save to tip Bruno Guimaraes’ shot onto the crossbar, before Leao hit the post with only Martin Dubravka to beat.
Word of a PSG comeback in Germany spread more nerves around the ground, while weary Newcastle legs offered hope of a Milan winner.
It was provided by Chukwueze, who took advantage of Fabian Schar’s involvement in a Newcastle attack by finishing a fluid Milan counter to silence St James’ Park.
Newcastle just couldn’t rouse themselves for a stirring finale and it was Milan who looked the most likely to score another, with Tomori striking the post and Theo Hernandez shooting wide after Dubravka had gone forward for a corner.
The final whistle was greeted by applause from the home fans, who were keen to acknowledge the efforts of their beleaguered players on a night that had promised so much but ultimately delivered so little.
Those supporters will always have the memory of thrashing PSG 4-1 in October - but it’s home defeats to Milan and Dortmund that have ultimately cost Newcastle.
Newcastle 1 - 2 AC Milan Howe: We can't focus on PSG penalty
Howe admitted he was "devastated" at Newcastle's elimination but insisted they cannot think what could have been had PSG not been awarded a controversial late penalty in the 1-1 draw in Paris last month.
Speaking to TNT Sports, Howe said: "We gave everything to the match. I couldn't ask any more of the players in terms of effort, commitment, physical exertion. Unfortunately for us, it wasn't to be.
"I thought there were some really good bits in our performance. We were dominant at times. We didn't defend the two goals well enough.
"It was very much end to end. Both teams were desperate to win. It made for a very good game.
Joelinton celebrates giving Newcastle the lead
Image: Joelinton celebrates giving Newcastle the lead
"It wasn't our best technical performance. We're not pleased with that on the night but we did create chances and we're devastated not to go through.
"It would be foolish of me to look back at that [PSG penalty] moment now and bring up old stuff. We had the opportunity tonight to do what we needed to do.
"But it's not through a lack of effort. I couldn't be prouder of what we've given physically and mentally, and we've given everything out on the pitch. We will learn from it and we will absorb everything we need to take into our Premier League form.
"We've learned so much, the value of the squad first and foremost. That has been what exposed us - the fact we haven't had the ability to utilise the squad we created and it has been a big frustration for us."
Merson 'worried' for Newcastle
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Eddie Howe
Kris Boyd believes Eddie Howe's job might be in danger following Newcastle's group-stage exit from the Champions League, but Paul Merson is adamant the Englishman has done brilliantly since joining the club in 2021
Sky Sports' Paul Merson speaking on Soccer Special:
"Newcastle got tired. They didn't know whether to stick or twist when they were 1-0 up.
"When PSG went 1-0 down in Dortmund, AC Milan got busier. All of a sudden, they could have gone through had they won and PSG lost.
"It then became too open. AC Milan opened the game up and there was shot after shot and no midfield and it was end to end.
"You looked at the quality of the players AC Milan brought on with fresh legs, and when Newcastle wanted to go gung-ho, they brought Alexander Isak on the left wing. He looked a bit lost out there on the left.
"In the end, Milan could have scored one or two goals. But the game changer was the Mike Maignan save from Bruno Guimaraes.
"Newcastle didn't really do enough to get out of this group - but it was a tough one. It wasn't like Man Utd's one. Anybody could have gone through in this one and anyone could have gone out, bar PSG.
"I'm a bit worried for Newcastle at the moment. They were a bit bare and they were a bit ahead of their time getting into the top four last year.
"If you look at last season, they had five or six players going to the max. Are they good enough players to produce that week in, week out, year in, year out? I'm not sure that's the case.
"At the moment, they could fall short in getting into the top four and next week's Carabao Cup quarter-final with Chelsea is now basically a cup final. Both teams need to win."
How Newcastle's exit harms England's coefficient
Hopes among Premier League sides were high at the start of the season that they would be in line for a fifth Champions League spot once the updated format is adopted next season.
With four extra spots available in the competition from the 2024/25 season, two will be provided to the countries with the two best UEFA coefficient rankings at the end of the current campaign.
UEFA coefficient ranking
Germany - 13.36
Italy - 13.14
England - 12.13
Spain - 12.06
France - 10.42
Two points are awarded to a country for every win their sides achieve in UEFA competitions, with one point for a draw.
Bonus points are earned for each stage to which a country's sides progress.
But with Newcastle following Manchester United out of Europe altogether, England have dropped behind Germany and Italy in the coefficient table.
That will be a tough gap to make up given 50 per cent of England's sides are already out of the Champions League, while Germany and Italy each have three sides in the last 16.
Opta stats: Miley breaks Walcott's record
Newcastle have finished bottom of a Champions League group for the first time, while it’s the second time in 2023/24 an English team has finished fourth (also Man Utd) - only one time fewer than in all other seasons combined (Blackburn in 1995/96, Man Utd in 2005/06 and Man City in 2012/13).
Newcastle have lost consecutive home matches in major European competition for the first time, losing to Borussia Dortmund in October and Milan tonight.
At the age of 17 years and 226 days, Newcastle’s Lewis Miley became the youngest player to assist a goal for an English club in Champions League history, breaking Theo Walcott’s record (17 years, 250 days in November 2006 for Arsenal).
Miley became only the fourth Englishman to start more than one Champions League game before turning 18, along with Josh McEachran (2), Phil Foden (2) and Jude Bellingham (8).
