This season she joined Peter Schmeichel, Carlos Tevez, Andy Cole and Abbie McManus amongst the list of stars that have celebrated derby success with both Manchester sides.
The 26-year-old defender has been an influential member of this current United team and they sit five points behind leaders Arsenal in the Women's Super League.
Mannion is back playing her best football after reuniting with head coach Marc Skinner who managed her at Birmingham City.
Skinner's side have established themselves as the one of the best defensive sides in the division with only Arsenal, Chelsea, and Tottenham conceding less.
Mannion signed for the Red Devils before she was released by Man City last summer and will be looking to prove a point against her former employers once again after a win over them in the League Cup earlier this season.
Her time at City was short-lived as she suffered an anterior cruciate ligament (ACL) injury in October 2019 which kept her out for 16 months.
She played just 11 times for the Citizens due to injury and the COVID-19 pandemic meant a return to fitness was a long-time coming.
The former City player told Sky Sports earlier this season: "It was a struggle two-fold - just the length of the injury lay-off and also that the rehab straddled the pandemic.
"I did a lot of my rehab in my parents' garden so I think everyone feels like a different person coming out of the pandemic and that's the same for me. Coming back from that means I don't take for granted being able to play.
"We played a pre-season match in Scotland and I had to remind myself that it was only the third full game I'd played since 2019, obviously due to the pandemic and then the injury. I really feel like a new kid at school, just finding my feet and really enjoying each game as it comes, which is a shift in perspective on how I'm seeing things."
Mannion has only won the FA Women's National League Cup, a competition equivalent to the EFL Trophy, with Aston Villa in 2013, but silverware with United can't be ruled out.
With the Midlands side, she was regarded by her former manager Joe Hunt as 'strong and aggressive' which she believes is down to her background in another sport.
She told Aston Villa's official website: "I play a lot of gaelic football still for a team called Sean McDermott's Ladies. I have been with them for a good few years.
"So it's instilled in me - that aggression - because the game is a mix between football and rugby. It's definitely a lot more physical and aggressive than football so you have to be able to hand yourself.
"Another key factor in my positive approach is that I played football for a boys team for three or four years. It was Celtic Reds, under Mark Fogarty's management.
"You have to be made of stern stuff to play against lads and we were successful too. Before I moved to Blues centre of excellence we won the Warwickshire County League and I was captain."
During her time at Birmingham City, she formed one of the best defensive partnership with Kerys Harrop in the division.
The defensive pair helped the West Midlands side to reach the 2014 Champions League semi-finals and finished third in the WSL in 2016 - agonisingly missing out on the league title by a single point to Liverpool.
In the following season, Birmingham lost 4-1 to Man City in the FA Cup final at Wembley as she failed to deliver any piece of silverware at the West Midlands.
Under Skinner's stewardship at Birmingham, she was selected in PFA Teams of the Years in her final two campaigns at the club.
Despite being a former Man City player, Mannion was classmates with England superstar Jack Grealish at St Peter's school in Solihull before they embarked their own journeys in professional football.
The England international also participated in gaelic football and competed against Mannion, playing for a rival opposition.
Mannion said: "I was in the same school as Jack. I sat next to him. I also played gaelic football against him. He played for a rival team.
"I remember him being a good footballer at school but I haven't seen much of him at Villa (in 2012)."
Both stars have had the rough and the smooth with Grealish suffering relegation to the Championship with Aston Villa.
But now both are battling to the top of the game with Mannion recovering from her lengthy ACL injury.
Meanwhile, the Manchester derby gives Mannion the perfect chance to remind Man City about her defensive qualities.
And she will look to help United register their first WSL win over their noisy-neighbours and seal a place amongst Manchester derby legends.