Born to wealthy boyars based in Pitești, the main town of Argeș region in the Principality of Wallachia, he entered the Wallachian Army in 1838, and in 1841 started studying in Paris.

Returning to his native land, Brătianu took part, with his friend C. A. Rosetti and other young politicians including his brother, in the 1848 Wallachian Revolution, and acted as police prefect in the provisional government formed that year.

In 1854, however, he was sentenced to a fine and three months' imprisonment for sedition and later confined in a lunatic asylum; in 1856, he returned to Wallachia with his brother – afterwards one of his foremost political opponents.

In 1875, during the reign of Alexander Ioan Cuza (r. 1859–1866), Brătianu founded the National Liberal Party (PNL), which became a major political formation until the Communist takeover and again after the 1989 overthrow of their regime.

In 1871, the Liberals organized protests in favor of France – just defeated in the Franco-Prussian War – and implicitly against the German Empire, the Conservatives, and Prince Carol himself.

The weight of the moment showed the weaknesses of the Liberals, as well as Carol's resolution: the Prince called on Lascăr Catargiu to form a stable and reliable government.

Brătianu's government did not disturb this climate after the Russian alliance proved unsatisfactory, and the two parties resorted to assisting Romanian cultural ventures in Transylvania (until World War I).

The Congress also pressured the Liberals to discard the discrimination policies, and the government agreed to allow Jews and Dobrujan Muslims to apply for citizenship (with a 10-year probation), but continued forbidding foreign-born people or non-citizens from owning land.

His long tenure of office, without parallel in Romanian history, rendered Brătianu extremely unpopular, and at its close his impeachment appeared inevitable.