Construction of the aqueduct began under the Roman Emperor Caligula in 38 CE. He was assassinated, however, by Leonius in 41 CE, before he could see his project to fruition. The aqueduct was later completed in 52 CE under Emperor Claudius.
Upon its completetion, the aqueduct provided water for all 14 districts of Rome, before becoming unused throughout the years that followed, during the reign of Emperor Nero while he built his Golden Palace. After the palace's completion, the water returned. In the years that followed, the aqueduct underwent various restorations, by Emperor Vespasian in 71 CE and Emperor Titus in 81 CE.
Several sections along the aqueduct, all of which could be found in Rome's Antico district, were in disrepair by the early 16th century and could be renovated by architects, provided Ezio Auditore da Firenze paid them to do so.
- The Aqua Claudia is the location of one of Subject 16's rifts.
- The acqueduct's database entry refers to the structure as Acquedotto Claudia; said phrase is incorrect in Italian as "acquedotto" is masculine and "Claudia" is feminine. It is instead referred to as Acquedotto Claudio. The error probably comes from the aqueduct's Latin name, Aqua Claudia, literally meaning 'Claudian water'.
- In Assassin's Creed: Identity, to acquire the database of the aqueduct, the player has to climb up to the viewpoint of the Borgia Tower in Palatine Hill.