Stephanie Frappart (second from left), officiated over the Women's World Cup final last month
Stephanie Frappart will referee the Uefa Super Cup final between Liverpool and Chelsea, becoming the first woman to take charge of a major men's European game.
Frappart will lead a team largely made up of female officials as the Champions League winners face the Europa League holders on 14 August in Istanbul.
In July, the Frenchwoman refereed the Women's World Cup final in Lyon.
Uefa president Aleksander Ceferin said he was "delighted" at her appointment.
"I have said on many occasions that the potential for women's football has no limits and I am delighted that Stephanie Frappart has been appointed to officiate at this year's Uefa Super Cup," Ceferin said.
Frappart will be joined by assistant referees Manuela Nicolosi (France) and Michelle O'Neal (Republic of Ireland), and fourth official Cuneyt Cakir (Turkey).
"As an organisation we place the utmost importance on the development of women's football in all areas," Ceferin added.
"I hope the skill and devotion that Stephanie has shown throughout her career to reach this level will provide inspiration to millions of girls and women around Europe and show them there should be no barriers in order to reach one's dream."
The 35-year-old took charge of the 2017 Uefa Women's Euro semi-final.
In April, Frappart created history domestically as she became the first female referee to officiate a Ligue 1 match before being promoted to join the pool of Ligue 1 referees on a permanent basis for the 2019/20 season.
"Stephanie has proved over a number of years that she is one of the best female referees, not just in Europe but across the world," said Uefa chief refereeing officer Roberto Rosetti.
"She has the ability to officiate on the biggest stage, as she proved at this year's Women's World Cup final. I hope this match in Istanbul will provide her with yet more experience as she enters the prime of her refereeing career."
Frappart follows the steps of former female referee Nicole Petignat of Switzerland, who officiated three Uefa Cup qualifying round games between 2004 and 2009.
BBC Sport has launched #ChangeTheGame this summer to showcase female athletes in a way they never have been before. Through more live women's sport available to watch across the BBC this summer, complemented by our journalism, we are aiming to turn up the volume on women's sport and alter perceptions. Find out more here.