Holders Bayern Munich will face the team they beat in last year's Champions League final in this season's quarter-finals after being drawn to play Paris St Germain.
In the other standout tie of the last eight 13-time champions Real Madrid face six-time winners Liverpool in a repeat of the 2018 final won by the Spanish club.
Runaway Premier League leaders Manchester City, seeking their first Champions League title, will play Borussia Dortmund with the winners to face Bayern or PSG in the semi-finals.
There is also the prospect of an all English semi-final after Chelsea were drawn to play Porto with the prize for the winners a clash with Real Madrid or Liverpool.
The Qatari owners of PSG have invested fortunes into trying to conquer the Champions League and came tantalisingly close last season when they reached the final only for Bayern's Kingsley Coman to break their hearts with the only goal in Lisbon.
Since then manager Thomas Tuchel has gone and been replaced by Mauricio Pochettino who took Tottenham Hotspur to the 2019 Champions League final where they lost to Liverpool.
Pochettino now faces a daunting task if he is to deliver the prize the Parisian club desire so badly.
Bundesliga leaders Bayern reached the quarter-final for a record 19th time by cruising past Lazio 6-2 on aggregate and will provide a formidable barrier.
Liverpool's Premier League title defence crumbled long ago but if anything can rouse the Anfield club it is a clash with Real Madrid in the Champions League.
Juergen Klopp's side are languishing in sixth place in the Premier League, 25 points behind Manchester City, and with no guarantee of a top-four finish they might need to win a seventh European crown just to get back in the competition.
Chelsea, unbeaten in 13 games since Tuchel replaced Frank Lampard, may feel they have got the easier option in Porto who they have beaten in five of their eight previous meetings.
Yet while Chelsea's clinical defeat of Atletico Madrid in the last 16 was impressive, so was the way Porto knocked out Juventus in a thriller and the Portuguese side will take that belief into their clash with the London club.
Should Chelsea and Liverpool both progress it would be the fourth time they have met in the Champions League semis.
Manchester City's Abu Dhabi owners have made winning the Champions League the priority in their masterplan and will feel this could be their year.
After a sluggish start to the season Pep Guardiola's side have dominated the Premier League and with that title virtually in the bag will be able to focus on Europe.
They sealed a fourth successive quarter-final berth with a 4-0 aggregate win over Borussia Moenchengladbach and have not conceded a goal in the competition for 11 hours 35 minutes.