Munster flyhalf Keatley has been picked ahead of Ian Madigan as mainstay Jonathan Sexton misses out after suffering a series of blows to the head.
Coach Joe Schmidt chose Jordi Murphy at number eight in place of vice-captain Jamie Heaslip (shoulder problem). Murphy will make his first start in the tournament.
O'Brien goes straight into the pack for his first test appearance since 2013, having made his comeback from shoulder reconstruction by playing 50 minutes for Ireland Wolfhounds against the England Saxons on Friday.
"Ian's combination with Conor Murray at Munster means they have a good understanding by playing together week by week," Schmidt said at the squad announcement on Thursday.
"It's a vote of confidence in Ian. His percentages of kicking success have been strong since Christmas so I have confidence he will kick well.
"Ian Madigan gives us that flexibility off the bench, being able to slot straight into number 12 or 10. It was a tight decision."
Ireland: 15-Rob Kearney, 14-Tommy Bowe, 13-Jared Payne, 12-Robbie Henshaw, 11-Simon Zebo, 10-Ian Keatley, 9-Conor Murray, 8-Jordi Murphy, 7-Sean O'Brien, 6-Peter O'Mahony, 5-Paul O'Connell (captain), 4-Devin Toner, 3-Mike Ross, 2-Rory Best, 1-Jack McGrath.
Replacements: 16-Sean Cronin, 17-James Cronin, 18-Martin Moore, 19-Iain Henderson, 20-Tommy O'Donnell, 21-Isaac Boss, 22-Ian Madigan, 23-Felix Jones.
(Story refiled to correct to Murphy making first Six Nations start, not debut)
(Reporting by Sam Holden, editing by Tony Jimenez)
