Holders Real Madrid will play Chelsea in the quarter-finals of the Champions League for the second season running, while Manchester City were paired with Pep Guardiola's former side Bayern Munich in Friday's draw.
Serie A leaders Napoli take on AC Milan in an all-Italian showdown and Inter Milan face Portuguese league leaders Benfica.
The winners of Real's tie against Chelsea will go on to face either City or Bayern in the semi-finals, throwing open the possibility of an all-English last-four tie.
That also increases the chances of seeing an Italian team reach the final for the first time since Juventus in 2017, as Inter will play either Milan or Napoli in the last four should the Nerazzurri beat Benfica.
Real's path to what would be a 15th European Cup is starting to look remarkably like last season, when they beat Chelsea and City before defeating Liverpool in the final.
Carlo Ancelotti's team are fresh from beating Liverpool in the last 16, and will now hope for a repeat of a year ago when they eliminated Chelsea 5-4 on aggregate in the quarter-finals.
The teams also met in the semi-finals in 2021, when the Stamford Bridge side won on their way to lifting the trophy for the second time.
City's ongoing bid to win the Champions League for the first time faces a major obstacle in a Bayern side who knocked out Paris Saint-Germain in the last round.
It will be the first encounter between the clubs since the 2014/15 group stage, when Guardiola was in charge of the German giants.
Guardiola left Bayern to join City in 2016, but is still chasing after a first Champions League title as a coach since winning it with Barcelona for the second time in 2011.
The draw appears somewhat lopsided, with the four richest clubs left in the competition all on the same side, while Italian clubs find themselves in the other half.
A year ago no Serie A side made it beyond the last 16, but now the runaway Italian league leaders Napoli will face the team who won the domestic title last season.
Napoli won 2-1 away to Milan in the league earlier this season and are due to host the seven-time European champions in Serie A on April 2, just a week and a half before the first leg of their Champions League tie.
Napoli are the only other club left in the competition other than City who have never won the trophy, while Inter's meeting with Benfica brings together two teams who have won it five times between them.
Benfica lost to Liverpool in the last eight a year ago and have never reached the semi-finals in the Champions League era.
Inter, currently second in Serie A, 18 points behind Napoli, have not reached the semi-finals since last winning the trophy under Jose Mourinho in 2010, the last victory for an Italian club in the Champions League.
The quarter-final first legs will be played on April 11 and 12, with Real entertaining Chelsea at the Santiago Bernabeu first before travelling to London for the return a week later, and City at home to Bayern first.
Inter were drawn to play Benfica at home initially but will now travel to Lisbon for the first leg to avoid a clash with Milan's meeting with Napoli at San Siro.
The semi-finals will be played in May with the final in Istanbul scheduled for Saturday, June 10.