Inter, who had already qualified for the next round, had 57 per cent possession and created 12 shots on goal to Benfica’s nine.
The home team took the lead in under five minutes when Joao Mario side footed home Casper Tengstedt’s clever header into his path.
Mario had his second eight minutes later when the ball ricocheted off two other players before rolling out to him for a finish from close range.
The Portuguese’s hattrick was complete in the 34th minute when a cross that wasn’t delt with by Inter found its way to him for another spectacularly easy finish into an empty net.
Inter came out firing after the break and got one back after six minutes when Marko Arnautovic was rewarded for his back-post run, getting on the end of Yann Bisseck’s header that had beaten the keeper but was going wide.
Seven minutes later Davide Frattesi made it 3-2 with a wonderful side-footed volley from Francesco Acerbi’s pinpoint cross.
In the 72nd minute, Alexis Sanchez completed the incredible comeback by slotting home a penalty awarded for a trip on Marcus Thuram.
Benfica’s Antonio Silva was shown a straight red with six minutes of regular time remaining thanks to a VAR upgrade from the initial yellow given for a reckless challenge on Nicolo Barella.
Inter are second in their group, level on points with Real Sociedad.
