The Portugal winger severely sprained his right ankle in Wednesday's 3-0 Champions League win over Marseille, in which he scored two goals.
Ronaldo has scored nine goals in seven games, including five in the league to help Madrid start the season unbeaten after five rounds.
"It's a significant loss," Madrid coach Manuel Pellegrini said on Saturday. "But we have a great squad that is ready for when these moments arrive, and the alternatives are very important."
Pellegrini also left midfielders Lassana Diarra and Fernando Gago, striker Ruud van Nistelrooy and defender Alvaro Arbeloa out of the squad.
Captain Raul Gonzalez or Argentina striker Gonzalo Higuain is expected to fill in for Ronaldo, who joined Madrid for euro94 million ($135 million) from Manchester United in the offseason.
Sevilla is third and has won six straight matches in all competitions, and forward Adriano is happy Ronaldo will be out.
"That works well for us," the Brazilian said. "But Madrid is always dangerous, whoever comes."