Alan Shearer's first-leg winner looked even more crucial when Kieron Dyer gave Newcastle what appeared an all-important away goal after 20 minutes to double the aggregate lead.
It meant that Sporting had to score three times to win the tie. They not only did that - they even managed a fourth as Graeme Souness saw his side fall to pieces in one of United's heaviest European defeats.
After a late first-half equaliser on the night from Romanian international Marius Niculae, strikes from Sa Pinto, central defender Beto and an injury-time fourth from the influential Fabio Rochemback left United doomed.
It was a nightmare start to Newcastle's biggest four days of the season and they now head to the Millennium Stadium for Sunday's FA Cup semi-final showdown with Manchester United needing a win to rescue their campaign.
With Laurent Robert left in the stands after unbelievably slagging off his team-mates, the pre-match build-up could not have been worse. And it now seems highly unlikely Robert will go to Cardiff.
United had to weather an early storm. Shay Given needed to be alert as Lisbon piled on the pressure and Steven Taylor's timely block denied the menacing Joao Moutinho after three minutes.
Carlos Martins flashed a 25-yarder wide as United defended stubbornly before hitting back and going in front after 20 minutes.
Having kept out a sliced clearance from the industrious Lee Bowyer, Given launched a long ball forward where Jermaine Jenas got a touch and Anderson Polga's poor control let in Dyer.
The England man charged forward and shot through the legs of Ricardo for the honour of netting Newcastle's 50th European away goal.
It could easily have been two when Alan Shearer cleverly broke on the right and pulled the ball back for Bowyer, but he was unable to keep his effort down.
Lisbon drew level five minutes before the break when Moutinho's cross from the right just flicked the head of Titus Bramble and Niculae headed in at the back post.
Given then pulled off a breathtaking save to deny Moutinho before at the other end, Shearer again played in the menacing Dyer whose effort beat Ricardo but ended up in the side-netting.
The second half was a nightmare for United as Souness was forced to use all three substitutes in the opening quarter hour. Jenas failed to appear after the break and off went the returning Bramble and the limping Dyer with a tweaked hamstring, to be replaced by James Milner, Andy O'Brien and Patrick Kluivert respectively.
Lisbon bombarded the United goal and were rewarded after 71 minutes when they levelled it up on aggregate at 2-2. Substitute Pedro Barbosa saw his shot beaten out by Given only for Sa Pinto to react first and bundle the ball over the line.
Shearer fired wide from 25 yards before Sporting grabbed their all-important third goal to go ahead for the first time in the two legs after 78 minutes. Central defender Beto climbed high to head in a Rochemback corner - Lisbon's ninth of the evening.
United had a golden opportunity to settle it on away goals two minutes from time, but Amdy Faye woefully volleyed a stunning Bowyer ball wide.
It was all over in the first minute of time added on when Stephen Carr was caught in possession by Rochemback and the Brazilian beat Given from just inside the box to make it 4-1.
A dejected Dyer said: "To concede four goals, you don't deserve to win a football match.
"For 60 minutes we were comfortable and then we blew a gasket.
"But the spirit is still good and now we've got to pick ourselves up for Sunday. It's our last chance of silverware and probably our last chance of getting back into Europe.
"Tonight our defending was not good enough and I'm not just blaming the defence. We did not defend as a unit.
"We had a great chance to win this tournament and only have ourselves to blame."