The 23-year-old former Chelsea and Blackburn Rovers forward, who has played for his country at under-20 level, has been in fine form this season scoring three Premier League goals.
Di Santo and recalled Newcastle United defender Fabricio Coloccini, a veteran of the 2006 World Cup, were included in a 23-man squad named by coach Alejandro Sabella for the November 14 match in Riyadh.
Espanyol goalkeeper Cristian Alvarez earned his first call-up and there were recalls for Benfica forward Eduardo Salvio, midfielders Ricky Alvarez of Inter Milan and Fabian Rinaudo of Sporting Lisbon as well as Olympique Lyon left back Luciano Monzon.
There was a first call to the full national squad for Celta Vigo midfielder Augusto Fernandez, who won two caps last year against Brazil in friendlies between sides picked from the countries' domestic leagues only.
Captain Lionel Messi could miss the match if his first son, due any day, is not born until close to that date, local media reported.
Goalkeepers: Sergio Romero (Sampdoria), Mariano Andujar (Catania), Cristian Alvarez (Espanyol).
Defenders: Hugo Campagnaro, Federico Fernandez (both Napoli), Fabricio Coloccini (Newcastle United), Pablo Zabaleta (Manchester City), Ezequiel Garay (Benfica), Marcos Rojo (Sporting Lisbon), Luciano Monzon (Olympique Lyon).
Midfielders: Javier Mascherano (Barcelona), Fernando Gago, Alberto Costa (both Valencia), Enzo Perez, Eduardo Salvio (both Benfica), Angel Di Maria (Real Madrid), Fabian Rinaudo (Sporting Lisbon), Augusto Fernandez (Celta Vigo), Ricky Alvarez (Inter Milan).
Forwards: Sergio Aguero (Manchester City), Lionel Messi (Barcelona), Gonzalo Higuain (Real Madrid), Franco Di Santo (Wigan Athletic).
Get the best features, fun and footballing frolics straight to your inbox every week.
Thank you for signing up to Four Four Two. You will receive a verification email shortly.
There was a problem. Please refresh the page and try again.