Nick Cushing's side will host Manchester United on 7/8 September 2019 in the first encounter since the league was formed.
The first competitive game between City and the original United Ladies took place in September 1990, with the Blues edging a 4-3 win, watched by over 150 at the University Grounds in the NWWRFL Div 2.
City will look to build on last season's cup double-winning success, having lifted both the FA Cup and Continental Cup, with skipper Steph Houghton and co. set to compete on all four fronts once again.
Georgia Stanway expressed her excitement for the eagerly-awaited season opener.
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"Everyone's really excited about playing in the Manchester Derby," she declared.
"Watching them growing up was always exciting and special for the fans and players involved. It means more than just three points and I can't wait to be involved in one.
"At the moment, of course, we're fully focused on the World Cup but it's the perfect way to kick off the new season and something to really look forward to."
Manager Cushing echoed: "We're really looking forward to the new season and kicking off with a Manchester Derby is a great way to start, especially following on from the World Cup.
"The prospect of a Manchester Derby has been on everyone's minds since Manchester United entered the FA WSL and it's going to be a great occasion for all involved.
"There's nothing quite like a local derby to concentrate everyone's focus as we look to build on our cup double-winning campaign."
Kelly Simmons, Director of the Women’s Professional Game, said: "It’s a very exciting time for women’s football with the country currently swept up in the FIFA Women’s World Cup and the Lionesses performing brilliantly.
"We’re looking forward to this increased interest carrying over into our domestic game next season and beyond.
“Opening weekend is packed full of great fixtures that are sure to set the tone for what promises to be the biggest and most exciting domestic season yet and we look forward to releasing the full fixture list next week."
The full fixture list across both leagues (the FA Women's Super League and FA Women's Championship) will be released on Wednesday 10 July.
Barclays FA WSL opening weekend fixtures: 7/8 September
Arsenal v West Ham United
Birmingham City v Everton
Bristol City v Brighton & Hove Albion
Chelsea v Tottenham Hotspur
Liverpool v Reading
Manchester City v Manchester United
FA WC opening weekend fixtures: 17/18 August
Aston Villa v Sheffield United
Crystal Palace v Coventry United
Leicester City v Durham
Lewes v Blackburn Rovers
London Bees v London City Lionesses
Free week: Charlton Athletic