Steph Catley, Caitlin Foord and Kyra Cooney-Cross all became queens of Europe with the boilover defeat of Barcelona in May, and after the club's disappointing start to their WSL season Arsenal's return to European action has taken on added importance.
But Sam Kerr and Ellie Carpenter's Chelsea are desperate to unseat their London rivals.
Though serial Women's Super League winners the Blues are yet to triumph in Europe - Kerr was in the side when they lost 4-0 to Barcelona in their only final in 2021.
Carpenter is a two-time winner, with Lyon, and will hope her experience helps Chelsea reach, then clear the final hurdle this time. Last year they lost to Barcelona in the semi-final losing both legs 4-1, the third successive year they have lost to the Catalan giants at that stage.
They face Barcelona again next month four but are at Dutch club Twente on Wednesday (0345 Thursday AEDT) with Kerr hoping to make her first start of the season.
However, after 91 minutes in four substitute appearances it is more likely she starts on the bench again as Chelsea continue to manage her comeback after 20 months out with her ACL injury.
Arsenal open against Teagan Micah's Lyon on Tuesday (0600 Wednesday AEDT), in a repeat of the semi-final won on aggregate by the Gunners last season.
Micah is yet to displace Chilean veteran Christiane Endler between the posts for the eight-time champions. Two fellow Matlidas are also yet to make a league start after summer moves - but hoping to figure in glamour opening ties on Wednesday (local time).
Wini Heatley's Roma are away to Real Madrid while Sharn Freier's Wolfsburg host Paris St-Germain.
Sarah Hunter's Paris FC host OH Leuven, the first Belgian club in the competition for 18 years, on Tuesday (local time).
This is the first year of a new format. Following the changes in the men's competition a year ago the women also play a league phase, with 18 clubs compared to the men's 36.
Teams that finish first to fourth in the standings advance directly to the quarterfinals. Those ranked fifth-12th go to a knock-out play-off round. The bottom six are eliminated.
This season also features the launch of a new second-tier competition, the Women's Europa Cup. This is a 16-club knock-out with Hayley Raso's Eintracht Frankfurt among the favourites.
Frankfurt, who fell into the competition after being losing in Champions League qualifying, face Czech side Slovacko in a two-leg final qualifying round tie with the first leg in Germany on Wednesday.
MATILDAS IN WOMEN'S CHAMPIONS LEAGUE
Arsenal: Steph Catley, Caitlin Foord, Kyra Cooney-Cross
Chelsea: Sam Kerr, Ellie Carpenter
Lyon: Teagan Micah
Paris FC: Sarah Hunter
Roma: Wini Heatley
Wolfsburg: Sharn Freier
