It is the latest in a line of firsts for the 39-year-old trailblazer from Washington, Tyne and Wear, who started refereeing in 2010.
A former NHS administrator who studied to be a referee with Durham County FA, Welch was the first woman to be appointed to take charge of an EFL match when League Two side Port Vale played Harrogate in April 2021.
She became a National Group Referee for the 2021/22 season and officiated Birmingham City's FA Cup third-round tie against Plymouth Argyle, again becoming the first woman to do so in the competition.
Welch was part of the Professional Game Match Officials Limited (PGMOL) Development Group last season, taking charge of two EFL Cup ties and two Championship matches.
This season she has been aligned to Select Group 2, and earlier this year FIFA appointed Welch to the officiating pool for the 2023 FIFA Women's World Cup in Australia and New Zealand.
She will become the fourth woman to be part of the team of officials for a Premier League match, following on from assistant referees Wendy Toms, Sian Massey-Ellis and Natalie Aspinall.
Massey-Ellis has herself already acted as a fourth official, taking over duties for the second half of West Ham United v Everton on 22 April 2017, after getting injured as an assistant referee.
Indeed, there will be two women officials featuring in the match as Massey-Ellis will be working as an Assistant VAR.
Welch, who has also overseen two Women's FA Cup finals, will be part of a four-strong team of match officials at Craven Cottage this weekend.
In the unlikely event that the referee John Brooks is unable to officiate after the match has started, such as sustaining an injury, Welch will step in to take charge and become the first woman to referee a Premier League match.