Drusus was born shortly after the divorce of his mother, Livia Drusilla, from Tiberius Claudius Nero; she immediately married Octavian (later Augustus), who was suspected of being Drusus' real father. Like his brother, Drusus was allowed to seek office five years before the legally specified age. He became praetor (magistrate) in 11 and consul in 9. With Tiberius he fought against two Alpine tribes (the Raeti and Vindelici), and in 13 he was made governor of the three Gauls. In this office he carried out an important census and erected the altar of Augustus at Lugdunum (now Lyon).

In 12–9 he led expeditions into Germany, establishing bases, first at Vetera (at the junction of the Lippe and Rhine rivers) and then at Mogontiacum (now Mainz). The Frisii, Chauci, Cherusci, and Chatti tribes were subdued, and a canal, the Fossa Drusiana, was dug from the Rhine to the North Sea. In the year 9, Drusus reached the Elbe River, but he was thrown from his horse and died of the injuries 30 days later. He was posthumously given the cognomen Germanicus. Drusus' conquests were extensive, but most were lost when Arminius defeated Publius Quinctilius Varus in the Battle of the Teutoburg Forest (AD 9). It was believed that Drusus desired the restoration of the republic, and his eldest son, Germanicus, was a popular favourite.

Drusus had married, about 16 BC, the younger Antonia, daughter of Mark Antony and Octavia. Their surviving children, besides Germanicus, were Livilla and Claudius, who later became emperor.