Simone Inzaghi's side were seen as the underdogs at the Estadio da Luz, but they travelled back to base with a 2-0 first-leg advantage to put one foot firmly in the final four.
Match preview
Enduring a six-game winless run in all tournaments before visiting Benfica's fortified headquarters, expectations were low for the Nerazzurri in last week's first leg, but a pair of crosses did the damage for Inzaghi's men during a steadfast showing.
Nicolo Barella and his 5ft 9in frame are not renowned for any sort of aerial prowess, but the midfielder nodded home from Alessandro Bastoni's pinpoint cross before Joao Mario was penalised for handball - Romelu Lukaku duly converted from the spot to double Inter's lead.
Knockout competitions have been Inter's speciality this season, as Inzaghi's side also prepare to take on Derby d'Italia foes Juventus in the second leg of their Coppa Italia semi-final later this month, but they have flattered to deceive in the top flight and went down 1-0 to regional rivals Monza at the weekend courtesy of Luca Caldirola's late goal.
Taking just one point from their last five Serie A matches means that the Nerazzurri are playing catch-up in the top-four face - sitting fifth in the rankings and two points adrift of fourth-placed AC Milan - who could await them in a tantalising European semi-final as they aim to complete their job against Napoli.
Each of the hosts' last three matches at San Siro has now ended in a 1-0 defeat - although they have not conceded more than once at home since a 2-1 loss to Roma in early October - and the three-time continental champions have never been eliminated from a European Cup knockout tie after winning the first leg by at least two goals.
It was not for the want of trying for Benfica last week, but a combination of wastefulness, Andre Onana and last-ditch Inter defending nullified Roger Schmidt's charges, whose Primeira Liga fortunes have also taken a nosedive as the weather warms up.
Potentially still reeling from a 2-1 loss to title rivals Porto a few days before hosting Inzaghi's men, Benfica's lead at the top of the rankings was cut down to just four points at the weekend, as mid-table Chaves stunned the Eagles 1-0 thanks to a stoppage-time strike from Issah Abass.
Arguably choosing the worst time to embark on a three-game losing run - they had not endured such a streak since November 2018 - the quarter-final curse could once again bedevil Benfica, who have never advanced to the semi-finals of the Champions League under its current name.
From the nine previous occasions in which they have lost the first leg of a European Cup knockout tie by at least two goals, Benfica have only progressed once - reversing a 3-1 deficit against Nurnberg to win 6-0 in the 1961-62 quarter-finals - and the Eagles ended up going all the way that year, beating Real Madrid in the showpiece match.
On a more optimistic note, Benfica have gone unbeaten in each of their last seven Champions League away games (excluding qualifying), but defeat in the first leg means that the Portuguese giants have failed to win any of their four meetings with Inter, with the only previous showdown at San Siro in 2004 ending in a 4-3 Nerazzurri success in the UEFA Cup.
Inter Milan Champions League form:
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W
L
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W
Inter Milan form (all competitions):
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L
D
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Benfica Champions League form:
D
W
W
W
W
L
Benfica form (all competitions):
W
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W
L
L
L
Team News
There was injury as well as insult for Inter in their lowly defeat to Monza, as centre-back Stefan de Vrij came off early in the second half with an ankle concern, but it is not yet clear how long the Dutchman may be sidelined for - Francesco Acerbi should return here in any case.
De Vrij is joined in the infirmary by fellow defender Milan Skriniar, whose back injury will reportedly not heal in time for the second leg, but Inzaghi has no other concerns to factor in and was able to welcome Hakan Calhanoglu back from a thigh problem at the weekend.
Marcelo Brozovic is expected to keep Calhanoglu out of the team for the time being, though, while Lukaku is going in search of his 10th Champions League goal in Nerazzurri colours - only four players have previously hit that landmark for Inter - but the well-rested pairing of Edin Dzeko and Lautaro Martinez could reform their attacking partnership.
While Inter are working without some experienced centre-backs, it is the opposite for Benfica, who will have Argentinian World Cup winner Nicolas Otamendi back from a ban served in the first leg; Morato is primed to drop out of the XI.
Midfielder Florentino is also available after missing the loss to Chaves through suspension, but Julian Draxler and Mihailo Ristic are both nursing muscular problems and appear set to miss out, while right-back Alexander Bah is facing at least a few more weeks out with a knee injury, so Gilberto continues in the Eagles' backline.
No striker has made more pressures in the final third than Goncalo Ramos's 299 for Benfica in the current Champions League campaign, and the 21-year-old is aiming to break a three-game goal drought at San Siro, having already netted 25 times in all tournaments this term.
Inter Milan possible starting lineup:
Onana; Darmian, Acerbi, Bastoni; Dumfries, Barella, Mkhitaryan, Brozovic, Dimarco; Dzeko, Martinez
Benfica possible starting lineup:
Vlachodimos; Gilberto, A. Silva, Otamendi, Grimaldo; Florentino, Aursnes; Neres, R. Silva, Mario; Ramos
We say: Inter Milan 1-1 Benfica (Inter win 3-1 on aggregate)
A depleted Inter backline that used to pride themselves on clean sheets should be breached on at least one occasion here, as Schmidt's side go for broke to keep their European dream alive.