He was known to have been a legate of Caesar's since about 54 BC, and served as an envoy to Pompey in 50. During the Roman Civil Wars he served in Spain, he might have been a tribune in 48, and in 47 was at Antioch. He was a praetor in 46 and governor of Transalpine Gaul in 45. Caesar had nominated Hirtius and Pansa for the consulship for 43; after the assassination, Hirtius was deeply involved in the maneuvering between parties.
Initially a supporter of Mark Antony, Hirtius was successfully lobbied by Cicero, who was a personal friend, switched his allegiance to the senatorial party, and set out with an army to attack Antony, who was besieging Mutina. In concert with Octavian, Hirtius compelled Antony to retire, but in the fighting Hirtius was slain (around 25 April or 27 April). He was honored with a public funeral, along with Pansa, who had been killed a few days earlier.
Hirtius added an eighth book to Caesar's De Bello Gallico, and is the likely author of Bellum Alexandrinum. The ancients thought he also wrote the Bellum Africum and Bellum Hispaniense, but it is now considered more likely that he acted as an editor. Hirtius' correspondence with Cicero was published in nine books, but has not survived.