Borussia Dortmund man Schulz, 26, played the full 90 minutes of Germany's 4-2 defeat to the Netherlands in Hamburg on Friday evening, before the diagnosis on Saturday cut short his international break.
Ahead of the crunch table-topping clash minnows Northern Ireland lead Group C on 12 points from four games, while Germany have nine from four games and Netherlands six from three.
According to the DFB, the wide man has torn a ligament in his favoured left foot, and will therefore not make the trip to Belfast with the rest of the squad.
Schulz has played a prominent role in Germany's recent resurgence since scoring on his international debut in a friendly against Peru last September.
He also scored a dramatic late winner in Germany's 3-2 victory over the Netherlands in Amsterdam last March, which he later said was "the most important goal in my career".
In Hamburg on Friday, he played as one of two wide players doubling up as wingers and full-backs in Joachim Loew's 5-3-2 system, which has faced fierce criticism in the wake of the 4-2 defeat.