Rebecca Welch will become the Premier League's first female referee when she oversees the match between Fulham and Sheffield United on 23 December.
Welch has been refereeing for 13 years and recently served as fourth official for Manchester United's trip to Craven Cottage.
She has refereed throughout the Football League, in the Women's Super League and at the Women's World Cup this summer.
During last month's Championship match between Birmingham City and Sheffield Wednesday at St Andrew's, two home supporters were arrested for misogynistic chanting directed towards Welch.
Another notable refereeing appointment sees Sam Allison become the Premier League's first black referee for 15 years.
Allison, a former firefighter, has been refereeing in the Football League since 2020 and was promoted to working on Championship games earlier this year.
"These are pivotal moments for Rebecca and Sam, who are two officials of real quality. They deserve their opportunity," said chief refereeing officer Howard Webb, speaking to BBC Sport.
"Rebecca has been exposed to some big games and I am really confident she will deliver a game in the Premier League and be a really good model for women and girls to think refereeing is for them.
"Sam deserves his chance as well. Maybe that will serve as a role model for other young people who maybe previously thought refereeing might not be for them.
"Hopefully they can show that refereeing can be for anybody - if you have the love of the game and the qualities required, you can make it to the very top."