Joy Neville will become the first female television match official for a top-level men's rugby union Test when Wales face Georgia on 21 November.
Neville refereed the Women's Rugby World Cup final in 2017 and was named World Rugby Referee of the Year.
The former Ireland captain has already refereed top-flight men's matches in European and Pro14 club competitions.
Meanwhile, Nigel Owens will become the first person to take charge of 100 Tests when France face Italy.
Both matches will be part of the Autumn Nations Cup, with France taking on Italy on 28 November.
Owens' first appointment of the competition will be at Twickenham on 14 November as England host Georgia.
"I hope it (100 games) will be achievable by the end of November," said Owens.
"It will be something special. It will be a great honour and one I am looking forward to. It was something I thought I might have reached last summer if things had not happened with the lockdown and Covid-19.
"I am looking forward to getting out there. I have not hung about just to get the 100. I am still here because I would like to think I am still capable of performing at the top of my game on the international stage."
The Rugby World Cup 2015 final referee will reach his milestone in Paris two weeks later, 17 years after his Test debut in February 2003 when he was in the middle for Portugal versus Georgia.
Elsewhere, former Harlequins scrum-half Karl Dickson - who is a regular official in the English Premiership - will take charge of his first major Test when France play Wales on 24 October.
Former Scotland sevens player Mike Adamson will referee his first major match when England face the Barbarians at Twickenham.