Ireland Sevens back Eve Higgins will make her Six Nations debut at centre in Saturday's opener against Wales in Cardiff.
Head coach Adam Griggs has also included uncapped backs Emily Lane and Stacey Flood in his 23-player squad.
Eimear Considine returns at full-back with Beibhinn Parsons lining out on the left in the other two changes from Ireland's win over Italy in October.
Ireland did not have a match last weekend, with Wales beaten by France.
Higgins, capped 20 times for Ireland Sevens, partners Sene Naoupu in midfield with Hannah Tyrrell and Ulster's Kathryn Dane retained at half back.
While Higgins' fellow Sevens internationals Flood and Lane are named among the replacements, there is no place for Grace Moore or Amee-Leigh Murphy Crowe, the top try scorer in the 2019 World Rugby Sevens.
Lindsay Peat, Cliodhna Moloney and Linda Djougang line out in the front row with captain Ciara Griffin leading the side at number eight.
"We are extremely confident in the squad we have selected," said Griggs.
"We have had a great deal of time to prepare together and this group of players have earned the responsibility to bring the high standards we have set ourselves throughout training into this first game.
"Wales at home will bring a strong challenge and we need to make sure we start the game well and build a platform that allows us to play our game and start this competition off with a win."
Ireland: Eimear Considine (Munster); Lauren Delany (Sale Sharks), Eve Higgins (Leinster), Sene Naoupu (Leinster), Beibhinn Parsons (Connacht); Hannah Tyrrell (Leinster), Kathryn Dane (Ulster); Lindsay Peat (Leinster), Cliodhna Moloney (Wasps), Linda Djougang (Leinster), Aoife McDermott (Leinster), Nichola Fryday (Connacht), Dorothy Wall (Munster), Claire Molloy (Wasps), Ciara Griffin (Munster).
Replacements: Neve Jones (Ulster), Katie O'Dwyer (Leinster), Laura Feely (Connacht), Brittany Hogan (Ulster), Hannah O'Connor (Leinster), Emily Lane (Munster), Stacey Flood (Leinster), Enya Breen (Munster).