Pepe was born at Squillace in Calabria.

He entered the army at an early age, but in 1799 he took part in the Neapolitan Republic, inspired by the French Revolution. He fought against the Bourbon troops under Cardinal Ruffo, was captured and exiled to France. He entered Napoleon's army and served with distinction in several campaigns, including those in the Neapolitan kingdom, first under Joseph Bonaparte and later under Joachim Murat.

After commanding a Neapolitan brigade in the Peninsular campaign, Pepe returned to Italy in 1813, with the rank of general, to help  reorganize the Neapolitan army. When the news of the fall of Napoleon (1814) reached Italy Pepe and several other generals tried without success to force Murat to grant a constitution as the only means of saving the kingdom from foreign invasion and the return of the Bourbons.

On Napoleon's escape from Elba (1815) Murat, after some hesitation, placed himself on the emperor's side and waged war against the Austrians, with Pepe on his staff. After several engagements the Neapolitans were forced to retire after the Battle of Tolentino (to which Pepe participated), and eventually agreed to the Treaty of Casalanza by which Murat was to abandon the kingdom; but the Neapolitan officers retained their rank under Ferdinand IV, who now regained the throne of Naples.

While engaged in suppressing brigandage in the Capitanata, Pepe organized the carbonari into a national militia, and was preparing to use them for political purposes. He had hoped that the king would grant a constitution, but when that hope failed he contemplated seizing Ferdinand, the emperor of Austria, and Metternich, who were expected at Avellino, and thus compelling them to instil a liberal constitution in Italy (1819). The scheme broke down through an accident, but in the following year a military rising broke out, the mutineers cheering for the king and the constitution. Pepe himself was sent against them, but while he was hesitating as to what course he should follow Ferdinand promised a constitution (July 1820). A revolt in Sicily having been repressed, Pepe was appointed inspector - general of the army.

In the meanwhile the king, who had no intention of respecting the constitution, went to Laibach to confer, with the sovereigns of the holy alliance assembled there, leaving his son as regent. He obtained the loan of an Austrian army with which to restore absolute power, while the regent dallied with the Liberals. Pepe, who in parliament had declared in favor of deposing the king, now took command of the army and marched against the Austrians. He attacked them at Rieti (March, 1821), but his raw levies were repulsed.

The army was gradually disbanded, and Pepe spent several years in England, France and other countries, publishing a number of books and pamphlets of a political character and keeping up his connection with the Carbonari. When in 1848 revolution and war broke out all over Italy, Pepe returned to Naples, where a constitution had again been proclaimed. He was given command of the Neapolitan army which was to co-operate with Piedmont against the Austrians, but when he reached Bologna the king, who had already changed his mind, recalled him and his troops. Pepe, after hesitating between his desire to fight for Italy, and his oath to the king, resigned his commission in the Neapolitan service and crossed the Po with 2,000 volunteers to take part in the campaign. After a good deal of fighting in Venetia, he joined Manin in the siege of Venice and took command of the defending army. When the city was forced by hunger to surrender to the Austrians, Pepe and Manin were among those excluded from the amnesty.

He again went into exile and died in Turin in 1855.