The Gunners will be looking to avoid a fourth consecutive loss in the WSL when they travel to Leigh Sports Village.
The match will see Russo face her former club for the first time since she made a free transfer move over summer.
And one former teammate in particular will be looking to ruin Russo's return as she aims to keep another clean sheet.
Manchester United's goalkeeper Earps set a new WSL record last season as she kept a total of 14 clean sheets - a feat which earned her team their highest ever finish.
Meanwhile, Russo scored 10 goals in the WSL last season and she finished joint-fifth in the race for the Golden Boot.
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Her performances also saw her crowned Manchester United Women's Player of the Year for the 2022/23 season.
But while Earps and Russo combined forces to make a commanding Manchester United side last season, this season will see them turn on each other.
The pair, though, could have linked up again in north London with Arsenal failing in a bid to sign England's No.1.
Instead, we're left with an exciting contest as England's best shot-stopper goes head-to-head with England's best shot-taker.
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Last season, it was Marc Skinner's side who proved the stronger of the two as Arsenal lost both their fixtures against Manchester United.
They lost their home fixture 2-3 at the Emirates after Russo - at the time playing for Manchester United - scored an injury-time winner.
It was Russo again who broke Arsenal hearts during the away game after she scored the only goal to give Manchester United a 1-0 victory.
But both clubs have seen a radical change of personnel during the summer transfer window.
Arsenal's manager Jonas Eidevall has brought in the likes of Swedish defender Amanda Illestedt and Australian midfielder Kyra Cooney-Cross alongside Russo, while Manchester United have signed a host of international talent including World Cup winner Irene Guerrero.
When the sides kick-off at Leigh Sports Village, the teams could look almost entirely different to the ones who faced each other last season.
Replacing Russo: United's attacking options
Despite losing Russo, Manchester United are by no means short of world-class attacking options.
Fans were treated to their first glimpses of Brazilian international and former Barcelona player Geyse in action against Aston Villa.
Geyse was absolutely unstoppable up front, her speed and flair causing endless problems for her defenders - a sure promise of what she could bring to the WSL.
Meanwhile, fan-favourite Leah Galton continues to perform for the Reds, leaving England fans to rue her decision to withdraw from international duty.
Galton has scored 31 goals in her 85 appearances for Manchester United.
She made herself unavailable for international duty in 2019 and, despite being approached by Sarina Wiegman, she reiterated her decision in 2022 to the disappointment of all England fans.
We are yet to see 2023 World Cup Golden Boot winner Hinata Miyazawa in action for Manchester United but her five goals for Japan over the summer speak volumes of her potential.
Rachel Williams and Nikita Parris also offer strong options off the bench for Manchester United.
Their best option off the bench could well be Lucia Garcia though - she scored the most goals of any substitute player in the whole WSL last season.
"She's not our player anymore"
Manchester United manager Skinner batted away questions about Russo in the pre-match press conference, insisting the focus was on beating Arsenal as a team.
He said: "In all honesty, I'm not really here to talk about Alessia. She's not my player."
He added: "I know that she returns and while Alessia was here, me and her had a really good relationship.
"She returns home and, of course, it's a narrative that we all want to spin but from my perspective, when we look at the forward that is now in place, she has different abilities to Alessia so...look Alessia is coming home and I absolutely understand the question but she's not our player anymore."
And Skinner was full of confidence that his team were capable of replicating and bettering their success in the WSL last season.
He said: "I get the rhetoric around it but I won't be making the narrative about Alessia. My narrative is about how my team can beat Arsenal. I'm confident in every game because I believe in this team and what they can do. I believe we can beat any opponent on any given day. We've shown that."
Skinner will also be preparing his team for their first ever Champions League match which takes place less than a week after their fixture against Arsenal.
They face a tough opening game as they host two-time Champions League runners-up PSG at Leigh Sports Village on Tuesday, October 10.
Russo a rare talent
But while Marc Skinner was keen to steer the conversation away from Russo, Arsenal manager Jonas Eidevall had no shortage of praise for the striker.
He said: "She has a lot of different qualities but what might be the unique thing is the combination of these qualities.
"Sometimes we have a forward that is loyal, extremely hard working in defence and you can live with that player not being so good technically, such as not being a good finisher.
"Sometimes you have a player who is a great finisher but you don't get exactly 100% in defence and maybe you can live with that for what it provides for the team's offence."
But Eidevall said the England striker's talent lay in her ability to excel in so many areas across the pitch.
He said: "She is a technical player but she can also control the duels and be really physical and protect the ball and it's very, very seldom you see a player that has all the aspects of it."
Russo has already scored two goals for Arsenal - both in the Champions League qualifying match against Paris FC which they ultimately lost.
Eidevall - who has just signed a new long-term deal with the north Londoners - will be hoping she can open her WSL scoring account and earn their first points of the season.
Will Mary Earps go to Arsenal in January?
While Manchester United have retained Earps for now, there is speculation that she could still join Russo in making the move to Arsenal.
Her contract expires next season and would leave her open to opportunities, particularly after two world-record bids were rejected by Manchester United in the summer.
And if the Red Devils do not sell Earps in January before her contract expires, we could even see her move as a free transfer, as Russo did.
Manchester United will, of course, be looking to get Earps to sign a new contract but their success could depend on how well they place in the WSL this season.
Earps has previously expressed that she is driven by her desire to compete at the top levels of women's football, especially in the Champions League.
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While she has her wish this season, if Manchester United fail to perform well in that competition, Earps could decide she is better-placed in a more established club.
One thing is for certain: Manchester United will lose one of the greatest players of this generation if they fail to secure Earps for the future.