Manchester United Women will play at Old Trafford for the first time when they take on West Ham in the Women's Super League on Saturday, 27 March.
The club, currently third in the table, have never played at the men's team's home since their reformation in 2018.
"Playing at Old Trafford will obviously be a special moment in the history of this team," boss Casey Stoney said.
"It's a fantastic opportunity to showcase the women's game, having seen huge growth in the past few years."
The match will be played behind closed doors because of coronavirus restrictions and comes during the men's international break, meaning the 76,000-capacity venue is free to be used.
The stadium is also due to be used in 2022 as England host the Uefa Women's European Championships.
"We are thrilled to be hosting our women's team at Old Trafford," said chief operating officer Collette Roche.
"The international break this month created a gap in this season's relentless programme at the stadium and we all agreed that this was the right time to welcome Casey and her squad to Old Trafford."
Manchester United Women have played their home games at Leigh Sports Village since the club was reformed in 2018.
Fellow WSL sides Manchester City, Chelsea, Tottenham, West Ham, Reading, Bristol City, Brighton and Aston Villa are among those to have played at least one home game at the grounds of their male counterparts over the past two seasons, while Liverpool and Everton hosted last season's Merseyside derbies at Anfield and Goodison Park respectively.