Iniesta and Cheryshev left out
Iniesta has failed to shine thus far and is replaced by Real Madrid's Marco Asensio as one of three changes made by Fernando Hierro.
Thiago and Dani Carvajal were also named on the bench with Nacho and Koke handed places in the starting XI.
Arguably more surprising was the decision taken by Russia coach Stanislav Cherchesov to leave out Denis Cheryshev.
Cheryshev has scored three goals in the tournament but is named among the substitutes.
Yuri Zhirkov, Mario Fernandes, Aleksandr Golovin and Daler Kuziaev come in.
TEAM NEWS!
Here's how #ESP and #RUS will begin in Moscow #ESPRUS pic.twitter.com/FtetYgKCtG— FIFA World Cup (@FIFAWorldCup) July 1, 2018