The visitors started positively, with El Hadji Malick Diouf volleying wastefully wide from Oscar Dorley’s flighted ball and David Doudera missing the target having been fed by Lukas Provod.
Doudera was then berating himself again after snatching at another Dorley cross before Diouf was dismissed on 26 minutes for catching Christian Pulisic’s right ankle with his studs up.
It didn’t take long for Milan to capitalise, as Rafael Leao’s attempted shot took a telling deflection off Tomas Vlcek to land perfectly on the head of Olivier Giroud, who nodded in from virtually on the goalline.
However, Slavia immediately hit back when Doudera stunningly volleyed past Mike Maignan, who was unable to keep the effort out despite getting a glove to it.
That equaliser shocked San Siro as Slavia goalkeeper Jindrich Stanek denied Matteo Gabbia with a superb reflex stop.
Tijjani Reijnders soon put his side back in front though, receiving Alessandro Florenzi’s pass unmarked on the edge of the area and giving Stanek the eyes to drive in superbly at the near post.
And on the stroke of half time, it was 3-1 as Florenzi’s sumptuous corner was finished from close range by Ruben Loftus-Cheek.
Not long after the break, a vital intervention from Lukas Masopust prevented Reijnders from doubling his tally for the evening. The pattern looked set for the evening, with Milan controlling proceedings.
However, out of the blue, Slavia halved the deficit on 65 minutes when substitute Ivan Schranz controlled well from Provod’s curling free-kick and slammed the ball past Maignan with aplomb.
Luka Jovic and Noah Okafor were subsequently thrown on to make things more comfortable for Milan, but Leao was the architect of the fourth, tying Vlcek up in knots before his dink over Stanek was stabbed in by Pulisic.
After a nervy encounter though, the Italian giants must look to strengthen a defence that has now conceded 10 times in five games ahead of the trip to Czechia for next Thursday’s return leg.
Flashscore Man of the Match: Lukas Provod (Slavia Prague)
Marseille romp to win, Rangers draw at Benfica
Marseille got their round-of-16 tie with Villarreal off to a flying start with a 4-0 win in their home leg thanks largely to a flurry of goals midway through the first half. The victory sets them up nicely to advance to the last eight.
Over in Lisbon, hosts Benfica had to come back to secure a 2-2 draw with in-form Scottish side Rangers. The Portuguese giants won't have it easy away in Glasgow next week.
Lastly, Freiburg edged West Ham 1-0 in their first-leg meeting in Germany.
