The 25-year-old, who was called up for Italy's Euro 2024 squad after an excellent end to the Serie A season, was injured during a friendly against Parma on Sunday.
"Gianluca Scamacca underwent diagnostic tests that revealed a rupture of the anterior cruciate ligament in his left knee," Atalanta said in a statement, indicating he was due to have surgery on Monday afternoon.
The club did not say how long he would be out of action but such injuries typically require four to six months of recovery time.
Scamacca joined Atalanta from West Ham in 2023, scoring 12 goals in 29 Serie A appearances.
He also scored six goals during Atalanta's run to the Europa League final where they beat Bayer Leverkusen.
Scamacca featured in all four of Italy's games at Euro 2024 which ended with a 2-0 defeat by Switzerland in the last 16.
