Hannah Jones will captain the team with a mix of experience and exciting young talent and will partner Kerin Lake, who will win her 50th cap for Wales, in the centre.
Lake, 34, made her Wales debut as a replacement against Scotland in 2011.
Fly-half Lleucu George completes the Wales midfield and will partner Keira Bevan at half-back, with Jenny Hesketh at full-back and Carys Cox and Lisa Neumann on the wings.
Gwenllian Pyrs, Carys Phillips and Sisilia Tuipulotu make up the Wales front row, with Abbie Fleming and Georgia Evans in the second row.
Vice-captain Alex Callender is at openside flanker with Alisha Butchers at blindside flanker, while Bethan Lewis is named at Number 8.
Wales and Spain have qualified for the new global WXV tournament but the winner of the clash in the Welsh capital will qualify for WXV2 in South Africa with the runner-up playing in WXV3 in Dubai.
Wales beat Italy 22-20 in the final game of the Women’s Six Nations front of a record 10,592 crowd at the Principality Stadium at the end of April.
Wales will face a Spain side that won the last Test match between the two sides 29-5 back in November 2019. Spain won their last Test match when they beat Sweden 53-0 in the European Championship.
Cunningham, said: “We know what we have to do – victory means World Cup qualification for England 2025 and qualification for WXV2 in South Africa in September.
“The focus all of this week has been on what we need to do and how we are going to play, and making sure we have the detail in our game right. We need to play with tempo and know Spain will view this vital game as a way to make a statement.
“We need to build on the win in our final game of the Guinness Six Nations against Italy and have selected the bulk of the team who delivered on that day. We know Spain have prepared with two warm-up games against Canada A and will pose a real challenge.
“Kerin Lake will win her 50th cap for her country and she is a popular and respected figure in the squad and the players will want to put in a performance to celebrate her achievement at international level.”
Wales squad to face Spain:
Jenny Hesketh, Lisa Neumann, Hannah Jones (captain), Kerin Lake, Carys Cox, Lleucu George, Keira Bevan; Gwenllian Pyrs, Carys Phillips, Sisilia Tuipulotu, Abbie Fleming, Georgia Evans, Alisha Butchers, Alex Callender (vice-captain), Bethan Lewis.
Replacements: Molly Reardon, Abbey Constable, Donna Rose, Kate Williams, Gwennan Hopkins, Sian Jones, Robyn Wilkins, Courtney Keight.
