Garry Ringrose out for Ireland's Six Nations opener against France
Ringrose was struggling with a shoulder issue ahead of selection, the Irish Times reported on Wednesday. Leinster teammate Robbie Henshaw will partner Bundee Aki in the centre for what promises to be a huge test of Ireland's title defence.
Crowley, the only one of the novice trio with any Six Nations experience with just three minutes against Italy last year, steps into the sizable boots of Johnny Sexton, who retired last year after a near unbroken 14-year run in the number 10 shirt.
While Nash's second cap comes as a result of a tournament-ending injury to Mack Hansen, McCarthy's fine club form and breakthrough at last year's World Cup put the big 22-year-old ahead of Leinster teammate James Ryan in the pecking order.
Elsewhere, Farrell retained 11 of the side that narrowly lost to New Zealand in October, having said he favoured retaining continuity over ripping up and starting again at the start of a new four-year World Cup cycle.
Farrell opted for a six-two split on the replacements bench, where Ryan Baird, Jack Conan and a fit again Cian Heal are among the forward contingent.
Munster flanker Peter O'Mahony leads the side having been appointed as Sexton's successor as captain earlier this month.
France earlier named Maxime Lucu at scrumhalf in place of Antoine Dupont, who is skipping the championship to prepare for the Olympics with the Rugby Sevens.
Ireland team:
15-Hugo Keenan, 14-Calvin Nash, 13-Robbie Henshaw, 12-Bundee Aki, 11-James Lowe, 10-Jack Crowley, 9- Jamison Gibson-Park, 8-Caelan Doris, 7-Josh van der Flier, 6-Peter O'Mahony (captain), 5-Tadhg Beirne, 4-Joe McCarthy, 3-Tadhg Furlong, 2-Dan Sheehan, 1-Andrew Porter
Replacements: 16-Ronan Kelleher, 17-Cian Healy, 18-Finlay Bealham, 19-James Ryan, 20-Ryan Baird, 21-Jack Conan, 22-Conor Murray, 23-Ciaran Frawley.