Octavianus (later Emperor Augustus) raised XV Apollinaris in order to end the occupation of Sicily by Sextus Pompeius, who was threatening Rome's grain supply.

After the conclusion of the war with Parthia, the legion was sent to Alexandria but soon found itself engaged in the fierce fighting of the First Jewish Revolt, capturing the towns of Jotapata and Gamla.

After the conflict was over the unit stayed in the east with a new headquarters at Satala in northeastern Cappadocia, with elements stationed at Trapezus on the Black Sea and at Ancyra, modern-day Ankara.

In 175, the general Avidius Cassius rebelled against Emperor Marcus Aurelius, but the Fifteenth remained loyal and earned the additional title Pia Fidelis.

As a unit stationed in the Middle East, it is almost certain to have taken part in later campaigns against Parthia, including the sack of its capital Ctesiphon by the Romans in 197, and in wars against the new Sassanid power that arose in Persia thereafter, though there is no direct record of this.