England head coach Eddie Jones had previously admitted he would rest some of the England players who went on this summer's British & Irish Lions tour of New Zealand, only to then name Mako Vunipola, Dan Cole, Courtney Lawes, George Kruis, Elliot Daly, Jonathan Joseph and Anthony Watson in his starting line-up for Saturday's Test.
However, Itoje and Farrell have been left out, with Exeter's Henry Slade handed Farrell's spot at inside centre, partnering Joseph in midfield.
Meanwhile, Saracens' Kruis comes in to the second row in place of Itoje to play alongside Northampton's Lawes against the powerful Pumas pack.
England have been boosted by Daly's recovery from a knee injury in time to feature but Jonny May misses out having failed to overcome a hamstring problem, Bath's Semesa Rokoduguni taking his place in the matchday squad.
Sam Underhill is one of seven England players to retain their places for the last Test match against Argentina, the 21-year-old starting at openside flanker after edging out 19-year-old Tom Curry.
Discussing his line-up for the autumn internationals opener, Jones said: "As a squad we have been preparing for this game since our first camp in August and are excited about playing in front of 82,000 fans at Twickenham Stadium on Saturday.
"This is our best 23 selected in what is our most important game this year. We know that Argentina is a strong team - Rugby World Cup semi-finalists in 2015 - and we will have to be smart and play well to beat them."
England XV: Mike Brown; Anthony Watson, Jonathan Joseph, Henry Slade, Elliot Daly; George Ford, Ben Youngs; Mako Vunipola, Dylan Hartley (capt), Dan Cole, Courtney Lawes, George Kruis, Chris Robshaw, Sam Underhill, Nathan Hughes.
Replacements: Jamie George, Ellis Genge, Harry Williams, Joe Launchbury, Tom Curry, Danny Care, Alex Lozowski, Semesa Rokoduguni.