The Manchester United striker, 37, has not been first choice for his club this season but will be part of his country’s bid to win the tournament for the first time in their history.
Ronaldo, the captain and all-time leading goalscorer in men’s international football with 117 strikes, has plenty of younger team-mates in support in attack, including Atletico Madrid’s Joao Felix and AC Milan’s Rafael Leao.
“All the players I have called up come with the hunger to win and make Portugal world champions, Ronaldo included,” said Santos.
The coach, who led Portugal to Euro 2016 glory in France, left Paris Saint-Germain midfielder Renato Sanches out of the squad, and called up Benfica centre-back Antonio Silva, 19, as well as veteran 39-year-old Pepe.
Wolves midfielder Joao Moutinho, 36, has appeared for his country 146 times, more than any other player apart from Ronaldo, was not included, and nor was his team-mate Goncalo Guedes.
Portugal open their World Cup campaign in Group H against Ghana on November 24, before facing Uruguay on November 28 and South Korea on December 2.
Goalkeepers: Diogo Costa (Porto), Rui Patricio (Roma/ITA), Jose Sa (Wolverhampton/ENG)
Defenders: Diogo Dalot (Manchester United/ENG), Joao Cancelo (Manchester City/ENG), Danilo Pereira (Paris Saint-Germain/FRA), Pepe (Porto), Ruben Dias (Manchester City/ENG), Antonio Silva (Benfica), Nuno Mendes (Paris Saint-Germain/FRA), Raphael Guerreiro (Borussia Dortmund/GER)
Midfielders: Ruben Neves (Wolverhampton/ENG), Joao Palhinha (Fulham/ENG), William Carvalho (Real Betis/ESP), Bruno Fernandes (Manchester United/ENG), Vitinha (Paris Saint-Germain/FRA), Otavio (Porto), Joao Mario (Benfica), Matheus Nunes (Wolverhampton/ENG), Bernardo Silva (Manchester City/ENG)
Forwards: Rafael Leao (AC Milan/ITA), Joao Felix (Atletico Madrid/ESP), Ricardo Horta (Braga), Goncalo Ramos (Benfica), Cristiano Ronaldo (Manchester United/ENG), Andre Silva