Sioned Harries is set to feature in her first Six Nations since 2018 after being named in Wales' squad.
Harries, 32, made her international comeback in Saturday's friendly against USA having won the last of her 58 caps in the 2019 autumn series.
Siwan Lillicrap captains the 37-strong squad, although faces a race for fitness after testing positive for Covid-19.
Wales open their championship in Dublin against Ireland on 26 March.
Outside-half Lleucu George is also back in the set-up and is announced as the latest player to sign a retainer contract with the Welsh Rugby Union (WRU).
Her last capped appearance was in March 2020.
Fresh faces
Wales head coach Ioan Cunningham has included six uncapped players in his squad, including Lowri Norkett who followed in the footsteps of younger sister Elli in playing for Wales last weekend.
Elli was tragically killed in a car accident in 2017, aged 20.
Norkett is joined by two other Wales-based players in Liliana Podpadec and Jenni Scoble, while Emma Hennessy, Emma Swords and Sisilia Tuipulotu are set to win their first caps.
Tuipulotu is a rising teenage star of women's rugby and the cousin of Wales men's number eight Taulupe Faletau.
Kayleigh Powell, Kelsey Jones and Gemma Rowland return to the squad after missing large parts of last season due to injury.
Wales will be targeting a first Six Nations win since 2019, and this year will be bolstered by professional players in their ranks.
Twelve players made history in January by signing the first full-time contracts with the WRU.
A further 12 - the latest being George - have agreed retainer deals, with three more due to be announced.
Wales can also take confidence from their autumn series in which they beat Japan and South Africa and threatened to claim the scalp of Canada, the fourth best women's side in the world.
Cunningham said: "We are pleased with the strength in depth within the squad given the tough challenge that is the TikTok Women's Six Nations.
"To start with Ireland away, Scotland at home and then the world champions England on their own turf over three consecutive weekends will certainly test us, but also give us the chance to develop as individuals and as a group.
"We are relishing the challenge."
A new era
It is fitting that Wales play their first competitive game with professionals against Ireland, as it was the 45-0 drubbing at the hands of the Irish in Cardiff last April that left Welsh women's rugby feeling at an all time low.
Lillicrap was in tears during post-match interviews, as calls for the WRU to do more to support the side reached fever pitch.
They included a scathing letter to the Union from over 100 former international players who demanded the reinstatement of performance pathways for females to play at elite level.
The Union commissioned a review and while the findings were not made public, it did admit to failings and apologised.
Nigel Walker was appointed WRU performance director in the autumn and made the women's game "front and centre" of his focus.
During his six months in charge he has overseen the long-promised contracts and the re-emergence of an under-18s regional and international set-up, in which Lillicrap was appointed skills coach under Liza Burgess.
Plans to bring back the under-20s are also in the pipeline for next season.
Walker said: "Our aim from the outset has been clear - to create a world class international programme that is competitive on the world stage. We aren't quite there yet but huge strides have already been made in a relatively short time.
"We now have 24 contracted players training within a professional programme. The environment we are creating around them will continue to evolve to a situation where the players will have everything elite athletes need to perform at the highest level.
"We won't rest while changes need to be made but we are satisfied with the sustainable measures we have put in place."
Making history
The Women's Six Nations will continue in its new spring window for a second year running.
It will also be played in its entirety this year after 2021 was shortened to a round-robin format amid the Covid-19 pandemic.
This year has also attracted a major sponsor in TikTok.
The social media platform, which also backs Hollywood-owned Wrexham football club, has signed a four-year deal as the women's tournament gets its own sponsor for the first time.
Wales Six Nations squad:
Forwards: Siwan Lillicrap (capt, Bristol Bears), Alisha Butchers (Bristol Bears), Alex Callender (Worcester Warriors), Gwen Crabb (Glouecster-Hartpury), Cara Hope (Gloucester-Hartpury), Kat Evans (Saracens), Abbie Fleming (Exeter Chiefs), Cerys Hale (Gloucester-Hartpury), Sioned Harries (Worcester Warriors), Natalia John (Bristol Bears), Manon Johnes (Bristol Bears), Kelsey Jones (Gloucester-Hartpury), Bethan Lewis (Gloucester-Hartpury), Liliana Podpadec (Llandaff North), Carys Phillips (Worcester Warriors), Gwenllian Pyrs (Sale Sharks), Donna Rose (Saracens), Jenni Scoble (Llandaff North), Caryl Thomas (Worcester Warriors), Sisilia Tuipulotu (Gloucester-Hartpury).
Backs: Keira Bevan (Bristol Bears), Lleucu George (Gloucester-Hartpury), Emma Hennessy (Cheltenham Tigers), Hannah Jones (Gloucester-Hartpury), Jasmine Joyce (Bristol Bears), Courtney Keight (Bristol Bears), Kerin Lake (Gloucester-Hartpury), Caitlin Lewis (Exeter Chiefs), Ffion Lewis (Worcester Warriors), Lisa Neumann (Gloucester-Hartpury), Lowri Norkett (Pontyclun), Kayleigh Powell (Bristol Bears), Gemma Rowland (Wasps), Emma Swords (Harlequins), Elinor Snowsill (Bristol Bears), Niamh Terry (Exeter Chiefs), Robyn Wilkins (Gloucester-Hartpury).