The 33-year-old sustained a calf muscle strain while playing for River Plate in Argentina's top flight and failed to recover in time for the Albiceleste's last two matches of 2024, the AFA said.
The entity did not immediately name a replacement for the former Fiorentina and Real Betis player. Pezzella's absence adds to the loss of Nicolas Gonzalez, who was already ruled out so he can keep recovering with Juventus in Turin.
The squad held their first practice, led by captain Lionel Messi, who got to the training center on Monday morning.
Argentina will meet Paraguay in Asuncion on Thursday and Peru in Buenos Aires five days later. The reigning World Cup and Copa America champion currently leads the South American qualifying zone with 22 points from 10 games.
