Regular skipper Hartley was been struggling with a calf injury and has failed to recover in time to keep his place in Eddie Jones' team, with Jamie George coming in at hooker in his absence.
Meanwhile, it will be centre Farrell who leads England out at the Stade de France, with prop Mako Vunipola named vice-captain, and Jones does not expect his team to lack leadership with the Saracens duo on the field.
"Owen will be very proud to be captain, but at the same time he is disappointed for Dylan to miss out through injury and he knows the position of captain carries a lot of responsibility," said Jones.
"We need to make sure we have one strong voice among the forward leaders and Mako has been doing some great work behind the scenes."
Elsewhere, fullback Mike Brown has been dropped after struggling in the defeat to Scotland last time out, with Elliot Daly replacing him in the starting XV and Anthony Watson shifting from the wing to fullback to accommodate the Wasps back's inclusion.
Ben Te'o has also been brought into the England side at outside centre, with Jonathan Joseph making way, while Jones has made a number of changes to his bench, naming Luke Cowan-Dickie, James Haskell, Sam Simmonds and Kyle Sinckler as replacements.
England team to face France: Watson; May, Te'o, Farrell (capt), Daly; Ford, Care; M Vunipola, George, Cole, Launchbury, Itoje, Lawes, Robshaw, Hughes.
Replacements: Cowan-Dickie, Marler, Sinckler, Haskell, Simmonds, Wigglesworth, Joseph, Brown.