Emma Hayes's side, who lost the 2020-21 final to Barcelona, qualified first from Group A with 19 points from their 21 matches against Paris Saint-Germain Women, Real Madrid Women and Vllaznia Women.
The Blues - who conceded just one goal throughout the group stage - have been rewarded for their endeavours with a last-eight tie against Lyon, who defeated Barcelona 3-1 in the 2021-22 final.
The first leg of the tie will be played at Lyon on March 21 or 22, before Chelsea welcome the holders to Stamford Bridge for the second leg one week later.
Despite their status as defending champions, Lyon could only finish second in Group C behind Arsenal, who will face Bayern Munich Women for a spot in the final four.
Jonas Eidevall's charges - who thumped Lyon 5-1 in the group stage - also beat Juventus and Zurich to a quarter-final berth, and they have one previous Champions League trophy to their name from the 2006-07 season.
Meanwhile, 2021 winners Barcelona Women - who finished above Bayern Munich in Group D - have been paired with Roma Women after the Italian side placed second in Group B.
Roma are making their first appearance in the Women's Champions League - having only been founded in 2018 - and their first leg against Barcelona will mark the inaugural game for the women's team at the Stadio Olimpico.
Finally, Group B winners Wolfsburg Women - who went through the opening phase of the competition unbeaten - are up against Paris Saint-Germain Women as the German team go in search of their third Champions League crown.
Wolfsburg got their hands on the prize in 2013 and 2014 and were most recently runners-up to Lyon in the 2020 final, while PSG lost the 2015 and 2017 finals to Eintracht Frankfurt and Lyon respectively.
The semi-final draw took place immediately after the quarter-final draw, and the winner of Lyon and Chelsea's tie will tackle Roma or Barcelona in the final four, while whoever wins out of Arsenal and Bayern will face PSG or Wolfsburg.
The 2022-23 Women's Champions League final will be played on June 3 at the Philips Stadion in Eindhoven.
WOMEN'S CHAMPIONS LEAGUE QUARTER-FINAL DRAW IN FULL:
Bayern vs. Arsenal
Lyon vs. Chelsea
Roma vs. Barcelona
PSG vs. Wolfsburg
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