The first leg was a home tie for Porto, but was played in Seville's Ramon Sanchez-Pizjuan Stadium due to coronavirus travel restrictions.
Thomas Tuchel would have already taken a 1-0 away win, but Ben Chilwell put the icing on the cake by pouncing on a mistake from Jesus Corona.
The second leg will also be played in Sevilla next week.
Despite holding a significant advantage heading into that game, the Blues must be wary of a Porto side which mustered 12 shots in the first leg, five of which were on target.
They will next face Crystal Palace at Selhurst Park on Saturday afternoon.