Byrne replaces captain Johnny Sexton, who sustained a hamstring injury in the first match of the tournament against Wales.
Second row James Ryan takes over as captain for the first time, while CJ Stander returns at blindside flanker and Peter O'Mahony will don the number seven shirt, with Caelan Doris selected at number eight.
Centre Bundee Aki replaces the injured Robbie Henshaw following the 32-9 win over Wayne Pivac's struggling Wales side, partnering Chris Farrell.
Jamison Gibson-Park retains his starting role at scrum-half, so Conor Murray will be on the bench once again for the clash with the Six Nations champions, who thrashed Georgia 40-0 last weekend.
Hugo Keenan gets the nod at full-back, with James Lowe and Keith Earls keeping their places on the wings.
Ireland: Hugo Keenan, Keith Earls, Chris Farrell, Bundee Aki, James Lowe, Ross Byrne, Jamison Gibson-Park; Cian Healy, Ronan Kelleher, Andrew Porter, Quinn Roux, James Ryan (captain), CJ Stander, Peter O’Mahony, Caelan Doris.
Replacements: Rob Herring, Ed Byrne, Finlay Bealham, Iain Henderson, Will Connors, Conor Murray, Billy Burns, Jacob Stockdale.