Chelsea knocked Real Madrid out in the semi-final stage of the competition en route to being European Kings for a second time in 2021 while Los Blancos exacted revenge by beating the Blues over two legs at the quuarterfinal stage last season.
It represents a second straight English opponent for Carlo Ancelotti's side in the knockout rounds of this season's competition after they beat Liverpool in the round of 16.
Chelsea saw off Borussia Dortmund 2-1 on aggregate to get this far.
Manchester City will do battle with Bayern Munich for a place in the quarterfinals. That means a return to the Allianz Arena for Pep Guardiola, who enjoyed a three-year stint in charge of the Bavarians.
Italian duo Napoli and AC Milan will square off for a spot in the last four.
Napoli earned a spot in the quarterfinals of the tournament for the first time in their history after comfortably dispatching Eintracht Frankfurt and have been rewarded with a date with the seven-time winners.
Benfica will face Inter Milan in the last quarterfinal tie.
The winner of the Chelsea-Real Madrid match will face Bayern Munich or Manchester City in the semi-finals while Inter Milan or Benfica awaits whoever comes out on top between Napoli and AC Milan.
The first legs of the quarter-finals take place on 11-12 April, with the return games on 18-19 April.
The first legs of the semi-finals will be on 9-10 May, and the second legs on 16-17 May.
The Ataturk Olympic Stadium in Istanbul, Turkey, will host the final on 10 June.