Number eight Siwan Lillicrap takes over as Wales captain from Carys Phillips when they face Ireland women in Dublin on Sunday.
Hooker Phillips drops to the bench after winning her 50th cap in the defeat by Spain last weekend.
Wales start with new caps in full-back Kayleigh Powell and wings Paige Randall and Courtney Keight.
Rebekah O'Loughlin could also make her debut off the bench while Ireland have six uncapped players in their squad.
Coach Rowland Phillips remains absent as he takes time away from the programme while his daughter Carys' starting place in the front row is taken by Ospreys' Kelsey Jones.
Set-piece coach Chris Horsman says Wales are keen to develop strength in depth as they build towards the 2021 World Cup.
"Our ultimate aim as a performance programme is to close the gap between ourselves and the best teams in international women's rugby," said the former Wales prop.
"We are ninth at the moment and we are determined to climb the rankings.
"In terms of the autumn series, we have a chance to develop our strength in depth given we are already qualified for the Rugby World Cup.
"However, at the end of the day it's a Test match and that will bring the challenges you'd expect from a Six Nations side."
Wales: Kayleigh Powell (Ospreys); Paige Randall (Cardiff Blues), Alecs Donovan (Ospreys), Robyn Wilkins (Cardiff Blues), Courtney Keight (Ospreys); Elinor Snowsill (Ospreys), Ffion Lewis (Scarlets); Gwenllian Pyrs (RGC), Kelsey Jones (Ospreys), Amy Evans (Ospreys), Natalia John (Ospreys), Gwen Crabb (Ospreys), Alex Callender (Scarlets), Bethan Lewis (Scarlets), Siwan Lillicrap (capt, Ospreys).
Replacements: Carys Phillips (Ospreys), Gwenllian Jenkins (Scarlets), Cerys Hale (Cardiff Blues), Sioned Harries (Scarlets), Robyn Lock (Ospreys), Keira Bevan (Ospreys), Megan Webb (Cardiff Blues), Rebekah O'Loughlin (Cardiff Blues).