Plisson, 23, comes in for injured first-choice No.10 Camille Lopez, who misses the game at Twickenham due to a knee problem.
With Sebastien Tillous-Borde remaining at scrum-half, it will be the 16th different half-back pairing Saint-Andre has picked in just over three years at the France helm.
The only other change sees Vincent Debaty come in for Eddy Ben Arous at prop after the latter suffered an injury to his arm.
Remi Tales and Uini Atonio replace Plisson and Debaty on the France bench.
France can still win the Six Nations but will need to not only beat England by at least eight points but also hope that Ireland lose in Scotland and Wales are beaten in Italy.
Team (15-1)
Scott Spedding; Yoann Huget, Gael Fickou, Maxime Mermoz, Noa Nakaitaci; Jules Plisson, Sebastian Tillous-Borde; Loann Goujon, Bernard Le Roux, Thierry Dusautoir (capt); Yoann Maestri, Alexandre Flanquart; Nicolas Mas, Guilhem Guirado, Vincent Debaty
Replacements: Benjamin Kayser, Rabah Slimani, Uini Atonio, Romain Taofifenua, Damien Chouly, Rory Kockott, Remi Tales, Mathieu Bastareaud.