The match will kick off at Olympiakos Piraeus' home ground in the Greek capital on 25 February.
The game, which was due to be held at the Emirates Stadium, was moved because Portugal is on the UK's 'red list', which means those arriving from the country must self-isolate for 10 days, with no exemptions for elite athletes.
The first leg will be held in Rome's Stadio Olimpico.
