The inclusion of Clerc, ruled out of the first two championship matches with a thigh injury, means Fofana can revert to centre after starting the games against Italy and Wales on the wing.
"We have made five changes (to the matchday squad) because it was important to regenerate physically and mentally," France coach Philippe Saint-Andre said.
"This is not a sanction for the players who are dropped. Against a powerful and efficient England team we want to send a commando unit to Twickenham."
Centre Maxime Mermoz, anonymous on Saturday when his side lost 16-6 at the Stade de France against holders Wales, has been omitted along with loose forwards Fulgence Ouedraogo and Damien Chouly, prop Yannick Forestier and lock Romain Taofifenua.
Chouly and Taofifenua started on the bench against Wales.
"Fulgence needs to have a scan on his right shoulder and we need our players to be 100 percent," added Saint-Andre.
"It is better Fulgence gets treatment so he can be at his best for the last two games of the championship (against Ireland and Scotland)."
Saint-Andre called up uncapped South African-born flanker Antonie Claassen and lock Christophe Samson who has made one previous appearance in a 49-10 win over Argentina in June.
Claassen can play at number six or eight.
"We have been following him for 15 months," said Saint-Andre. "He is well integrated and speaks French fluently after playing six years in France.
"I wish him the same success his predecessors had," he added, referring to the Moroccan-born Abdelatif Benazzi, New-Zealand born Tony Marsh and South African-born Eric Melville and Pieter de Villiers.
Flanker Yannick Nyanga, who missed the 23-18 defeat in Italy at the start of the month through injury, returns and loosehead prop Thomas Domingo is back after being dropped from Saint-Andre's initial 33-man squad.
Forwards: Vincent Debaty, Thomas Domingo, Benjamin Kayser, Dimitri Szarzewski, Luc Ducalcon, Nicolas Mas, Yoann Maestri, Christophe Samson, Jocelino Suta, Antonie Claassen, Thierry Dusautoir (captain), Yannick Nyanga, Louis Picamoles,
Backs: Maxime Machenaud, Morgan Parra, Frederic Michalak, Francois Trinh-Duc, Mathieu Bastareaud, Vincent Clerc, Benjamin Fall, Wesley Fofana, Florian Fritz, Yoann Huget