Farrell is picked at inside centre in place of Henry Slade, who drops to the replacements' bench, in one of two changes in personnel to the backline that helped topple the Pumas 21-8.
Jonny May's recovery from a hamstring strain sees him selected on the right wing while Mike Brown's failure to recover from concussion sees Anthony Watson start at full-back for the first time.
Maro Itoje was also rested against Argentina and must now settle for a place among the replacements, while Joe Launchbury is selected as Courtney Lawes' second row partner after George Kruis was dropped.
"I have selected the strongest 23 to play Australia and we will have to be effective in everything we do this weekend to win," head coach Eddie Jones said.
England team to play Australia at Twickenham on Saturday, November 18, 3pm KO:
A Watson (Bath); J May (Leicester), J Joseph (Bath), O Farrell (Saracens), E Daly (Wasps); G Ford (Leicester), B Youngs (Leicester); M Vunipola (Saracens), D Hartley (Northampton, capt), D Cole (Leicester), J Launchbury (Wasps), C Lawes (Northampton), Robshaw (Harlequins), S Underhill (Bath), N Hughes (Wasps).
Replacements: J George (Saracens), J Marler (Harlequins), H Williams (Exeter), M Itoje (Saracens), S Simmonds (Exeter), D Care (Harlequins), H Slade (Exeter), S Rokoduguni (Bath).
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