The Blues are back in the competition having missed out last season, and they face a team who are in the Champions League group stage for the first time in their history.
Here's everything you need to know about Tuesday's clash.
Date: Tuesday, September 12
Time: 7:45 p.m. BST/2:45 p.m. ET
Venue: Stamford Bridge, London
TV Info: BT Sport (UK), Fox Sports (U.S.)
Chelsea go into the game in good form after three consecutive Premier League wins and with Eden Hazard available after injury.
The Belgium international was introduced as a substitute in the 2-1 win over Leicester City on Saturday as he works his way back to full fitness after a broken ankle, and he may not start against Qarabag.
However, Chelsea manager Antonio Conte may use the same formation as for the win at the King Power Stadium, which would be a good option in Europe, according to Goal's Nizaar Kinsella:
Saturday's win also saw summer signing Davide Zappacosta make his Chelsea debut, and he could be involved in midweek, per ESPN FC's Liam Twomey:
One player who looks certain to start for Chelsea is Alvaro Morata, who has adjusted to life in England well with three goals already in the Premier League.
Morata was part of the Real Madrid squad that won the Champions League in 2014 and last season, and he will take some stopping on current form, as the competition's Twitter account noted:
Qarabag are the great unknowns of the group, although they have started their domestic season well with three straight wins.
They made it to the group stage via the qualifiers, where they saw off FC Samtredia of Georgia, FC Sheriff Tiraspol of Moldova and beat FC Copenhagen in the play-offs on away goals.
However, the Premier League champions are a different proposition altogether, and on home turf against opposition inexperienced at this level, the hosts will be expected to kick off their campaign with a comfortable win.