Conor Murray was left out of Ireland's squad for the November internationals to continue his recovery from a neck injury as coach Joe Schmidt named a 42-man squad Wednesday.
Murray has not played since Ireland's series-clinching victory over Australia in Sydney in June and his coach at Munster, Johann van Graan, said Tuesday he was still not ready to return.
The absence of the British & Irish Lions' scrumhalf will give John Cooney, Kieran Marmion and Luke McGrath a chance to stake a claim at the one position where Ireland are missing experienced depth.
Elsewhere flyhalf Ross Byrne, who was an unused replacement in the third test in Sydney, is likely to win his first cap next month. Irish-based and qualified Englishman Will Addison was also included for the first time.
"As always there have been a number of close calls in selection, meaning that some very good players have missed out in this particular window," Schmidt said in a statement.
"The upcoming tests offer an exciting opportunity for the squad but will also be very challenging."
Ireland begin their series with a trip to Chicago on Nov. 3 to face Italy before returning home for successive tests against Argentina, New Zealand and the United States.
The 2018 Grand Slam winners beat New Zealand for the first time in their last visit to Chicago two years ago, a victory that helped Schmidt's side move to second in the world rankings.
Full Squad
Backs (18): Will Addison (Ulster), Bundee Aki (Connacht), Sam Arnold (Munster), Ross Byrne (Leinster), Joey Carbery, Andrew Conway (both Munster), John Cooney (Ulster), Keith Earls (Munster), Robbie Henshaw, Rob Kearney, Jordan Larmour (all Leinster), Kieran Marmion (Connacht), Stuart McCloskey (Ulster), Luke McGrath, Garry Ringrose, Jonathan Sexton (all Leinster), Jacob Stockdale (Ulster), Darren Sweetnam (Munster)
Forwards (24): Rory Best (Ulster), Finlay Bealham (Connacht), Tadhg Beirne (Munster), Jack Conan, Sean Cronin, Tadhg Furlong, Cian Healy (all Leinster), Iain Henderson, Rob Herring (both Ulster), Dave Kilcoyne (Munster), Dan Leavy, Jack McGrath (both Leinster), Jordi Murphy (Ulster), Sean O'Brien (Leinster), Peter O'Mahony (Munster), Andrew Porter (Leinster), Quinn Roux (Connacht), Rhys Ruddock, James Ryan (both Leinster), John Ryan, Niall Scannell, CJ Stander (all Munster), Devin Toner, Josh van der Flier (both Leinster)