Sara Cox will become the first woman to referee two top-flight English teams when she takes charge of Northampton v Wasps in the Premiership Rugby Cup on Sunday.
Cox, 28, was made the world's first professional female rugby referee in March 2016 when she earned a central contract with the Rugby Football Union.
She was the first woman to officiate a second-tier men's game in England when she oversaw Cornish Pirates' meeting with Doncaster Knights in the Championship in March.
Cox, who gave up her own playing career because of injury, is scheduled to get her first experience of a men's international this autumn, working on the sidelines of Hong Kong v Germany and Kenya v Germany, while she will also take charge of France Women v New Zealand Women on 9 November.
Three other women will be part of the officiating teams in this round of the Premiership Rugby Cup with Claire Hodnett working as the television match official at Harlequins' meeting with Newcastle, Clare Daniels in the assistant referee role for Bristol's match against Gloucester and Danae Zamboulis acting as the citing officer for Leicester v Worcester.
Former Ireland international Joy Neville became the first female referee to oversee a top-level men's match in the UK in February when she took charge of Ulster's win over Southern Kings in the Pro14.