Centre-back Pepe will become the second oldest outfield player in World Cup history after he was picked to start for Portugal against Uruguay on Monday.
The 39-year-old comes in for the injured Danilo, who mysteriously suffered broken ribs, as one of three changes made by Portugal coach Fernando Santos.
Cameroon's Roger Milla remains the oldest outfield player to play in a World Cup at USA 1994 aged 42.
Two goalkeepers can beat that though.
Essam El-Hadary of Egypt was 45 when he played in Russia 2018 while Colombian shot-stopper Faryd Mondragon was 43 in Brazil 2014.
Nuno Mendes gets the nod over Raphael Guerreiro at left-back for Portugal and William Carvalho comes into midfield in place of Otavio.
Edinson Cavani was picked ahead of fellow Uruguay icon Luis Suarez in attack as coach Diego Alonso switches his formation from a back four to a back three.
Centre-back Sebastian Coates comes in with winger Facundo Pellistri dropping to the bench while Guillermo Varela is picked at right wing-back instead of veteran Martin Caceres.
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TEAMS:
Portugal:Diogo Costa, Joao Cancelo, Pepe, Ruben Dias, Nuno Mendes, Ruben Neves, Bernardo Silva, Bruno Fernandes, William Carvalho, Joao Felix, Cristiano Ronaldo.
Uruguay:Sergio Rochet, Sebastian Coates, Diego Godin, Jose Maria Gimenez, Guillermo Varela, Mathias Olivera, Rodrigo Bentancur, Matias Vecino, Federico Valverde, Edinson Cavani, Darwin Nunez.