O'Mahony has captained the side 10 times before having led Ireland at underage levels before winning his first of his 101 caps. He has also skippered Munster for years and captained the British & Irish Lions in the opening test of the 2017 tour.
O'Mahony got the armband ahead of new Leinster co-captains Garry Ringrose and James Ryan, who were included in the squad. Given his age, O'Mahony may well lead Ireland for the next couple of Six Nations rather than through to the 2027 World Cup.
"Ever since I was a boy starting off in the game, I have always dreamed of captaining Ireland," O'Mahony said in a statement.
"To be now asked to captain Ireland ahead of the Six Nations is without doubt one of the proudest moments of my life and I would like to thank Andy for this show of faith in me."
The Six Nations will have a number of new faces front and centre this year after England, France and Wales all named new captains this week, while Scotland have yet to decide on a skipper.
Farrell, who will have to take some time away from the Ireland role next year after he was appointed head coach of the 2025 Lions last week, praised O'Mahony as "a born leader" and a key figure for club and country for many years.
Already facing their first Six Nations in 14 years without their hugely influential former flyhalf Sexton, Ireland suffered a double injury blow last week when backs Mack Hansen and Jimmy O'Brien were ruled out of the tournament.
That meant Hugo Keenan and James Lowe were the only fullback and winger available from the World Cup squad, opening up spots for Leinster's Jordan Larmour, Ulster's Jacob Stockdale and Munster's Calvin Nash.
Munster's Jack Crowley appears poised to replace Sexton at flyhalf, with his main rival Ross Byrne also injured. Byrne's younger brother Harry and his Leinster team mate Ciaran Frawley, with three caps between them, are the other options at 10.
Farrell was able to choose an almost identical group of forwards to the World Cup, with Cian Healy also fit again, while he also opted not to include any uncapped players for the tournament that Ireland begin away to France on Feb. 2.
Ireland squad:
Forwards: Ryan Baird, Finlay Bealham, Tadhg Beirne, Jack Conan, Caelan Doris, Tadhg Furlong, Cian Healy, Iain Henderson, Ronan Kelleher, Jeremy Loughman, Joe McCarthy, Peter O'Mahony (captain), Tom O'Toole, Andrew Porter, James Ryan, Dan Sheehan, Tom Stewart, Nick Timoney, Josh van der Flier
Backs: Bundee Aki, Harry Byrne, Craig Casey, Jack Crowley, Ciaran Frawley, Jamison Gibson-Park, Robbie Henshaw, Hugo Keenan, Jordan Larmour, James Lowe, Stuart McCloskey, Conor Murray, Calvin Nash, Garry Ringrose, Jacob Stockdale
