Cuza's reform policies alienated a large coalition of conservatives and radical liberals, for the most part landowners and business owners.

Returning during the reign of Prince Grigore Alexandru Ghica, he became Moldavia's minister of war in 1858; he also represented Galați in the ad hoc Divan at Iași.

In default of a foreign prince, he was nominated as a candidate in both principalities by the pro-unionist Partida Națională (profiting of an ambiguity in the text of the Treaty of Paris).

The Powers backtracked, with Napoleon III of France remaining supportive, while the Austrian ministry withheld approval of such a union at the Congress of Paris (18 October 1858); partly as a consequence, Cuza's authority was not recognized by his nominal suzerain, Abdülaziz, the Sultan of the Ottoman Empire, until 23 December 1861.

The union was formally declared three years later, on 5 February 1862, (24 January Julian), the new country bearing the name of Romania, with Bucharest as its capital city.

Assisted by his councilor Mihail Kogălniceanu, an intellectual leader of the 1848 revolution, Cuza initiated a series of reforms that contributed to the modernization of Romanian society and of state structures.

[7] Probably more than a quarter of Romania's farmland was controlled by untaxed Eastern Orthodox "Dedicated monasteries", which supported Greek and other foreign monks in shrines such as Mount Athos and Jerusalem, presenting a substantial drain on state revenues.

Despite the attempts by Lascăr Catargiu's cabinet to force a transition in which some corvées were to be maintained, Cuza's reform marked the disappearance of the boyar class as a privileged group, and led to a channeling of energies into capitalism and industrialization; at the same time, however, land distributed was still below necessities, and the problem became stringent over the following decades – as peasants reduced to destitution sold off their land or found that it was insufficient for the needs of their growing families.

Cuza failed in his effort to create an alliance of prosperous peasants and a strong liberal prince, ruling as a benevolent authoritarian in the style of Napoleon III.

Having to rely on a decreasing group of hand-picked bureaucrats, Cuza began facing a mounting opposition after his land reform bill, with liberal landowners voicing concerns over his ability to represent their interests.

Along with financial distress, there was an awkward scandal that revolved around his mistress, Maria Catargiu-Obrenović, and popular discontent culminated in a coup d'état.

Despite the participation of Ion Brătianu and other future leaders of the Liberal Party in the overthrow of Cuza, he remained a hero to the radical and republican wing, who, as Francophiles, had an additional reason to oppose a Prussian monarch; anti-Carol riots in Bucharest during the Franco-Prussian War (see History of Bucharest) and the coup attempt known as the Republic of Ploiești in August 1870, the conflict was eventually resolved by the compromise between Brătianu and Carol, with the arrival of a prolonged and influential Liberal cabinet.