Lealiifano, 31, is set for his first Australia appearance since June 2016, having returned to form with the Brumbies after a battle with leukaemia.
While Lealiifano was named to start at fly-half for the Wallabies in the Rugby Championship clash in Brisbane on Saturday, O'Connor is among the reserves.
O'Connor has played 44 Tests for the Wallabies, but the last of those was in September 2013, also against Argentina.
— Qantas Wallabies (@qantaswallabies) July 24, 2019
Wallabies coach Michael Cheika made five changes to the starting team that lost to South Africa 35-17 and another five to his reserves.
Scott Sio is back from a hamstring injury for Australia, who have won 16 of their past 18 games against Argentina.
The Wallabies have also been hard to stop at Suncorp Stadium, where they have won their past five games, including four by a single-digit margin.
Australia: Kurtley Beale, Reece Hodge, Tevita Kuridrani, Samu Kerevi, Marika Koroibete, Christian Lealiifano, Will Genia; Scott Sio, Folau Fainga'a, Sekope Kepu, Izack Rodda, Rory Arnold, Lukhan Salakaia-Loto, Michael Hooper, Isi Naisarani.
Replacements: Tolu Latu, James Slipper, Taniela Tupou, Rob Simmons, Luke Jones, Nic White, Matt To'omua, James O'Connor.
Photo Getty Images. Caption: Brumbies playmaker Christian Lealiifano