Born to a political family in Tecuci, he was the nephew of Alexandru Bădărău, twice a minister in Conservative cabinets during the early 1900s, and a descendant of the Moldavian boyar known as Logofătul Tăutu [ro]; his grandfather was strong unionist, a supporter of the Union of Moldova with Wallachia, while his father was a member of the Socialist Party.

Having been the recipient of the Gazeta Matematică prize in 1910, he went on to study at the "Școala de Poduri și Șosele" (the School of Bridges and Roads) in Bucharest, completing his training as a valedictorian in 1915.

[10] In the autumn of 1927, while distributing Carol's appeals to the leaders of various political parties and carrying his letter to Queen Marie, he was arrested (martial law was proclaimed by the Ion I. C. Brătianu government in the incident's wake).

"[14]While accusing the executive of having previously attempted to purchase his silence, Manoilescu stressed his belief that King Ferdinand had, just before his death, asked Brătianu for Carol to be allowed to return.

[19] In his memoirs, Manoilescu claimed that, at the time, he had played a hand in the release of Mihai Gheorghiu Bujor (imprisoned since 1918, due to his Bolshevik activism and designs for a communist revolution);[20] Manoilescu authored a series of articles in his support, and allegedly intervened alongside King Carol[20] (it is generally accepted that the most decisive action in this respect was taken by Maniu, who spoke against imprisonment for political crimes such as Bujor's).

As governor, he refused to salvage the Marmorosch Blank Bank with state funds, and clashed with Carol over the issue, being ultimately removed from office in November of the same year.

[5] His intense advocacy of industrialization formed the main theme of the book The role and destiny of Romania's bourgeoisie (1942), which was one of the main works dealing with the development of a local middle class, alongside those written by Ştefan Zeletin and Eugen Lovinescu (while sharing some perspectives with the essays of Emil Cioran);[23] the topic blended with his support for authoritarianism and the one-party system, as Manoilescu rejected democracy (which, in his view, encouraged the majority-forming peasantry to decide on matters that did not concern it).

"[25]Among others, Manoilescu adopted some of the Poporanist ideas on capital and its international circulation, as present in the works of Constantin Stere[26] (in turn influenced by the Marxist Werner Sombart).

[28] At the same time, his magazine supported a nationalist and racist approach, viewing corporatism as "the guarantee of Romanianization",[29] and proclaiming that "the racial basis of Romania is the same as that of Aryan Europe".

[42] In February 1937, he began discreetly financing the Guard's newly created paper, Buna Vestire (he was exposed as the man behind it by virtually all political commentators of the time).

[19][44] According to his political adversary Constantin Argetoianu, the party's unofficial leader Corneliu Zelea Codreanu made similar proposals to philosopher Nae Ionescu and General Gheorghe Moruzi: Ionescu denied the request because, as a self-proclaimed pillar of the Guard, he could not accept such a lowly position, while Moruzi called Manoilescu "a con artist" and alluded to his reported connection with Magda Lupescu.

"[19] During the period, Manoilescu also applied changes to his earlier vision on industry and self-sufficiency, calling for Romania to develop itself by supplying raw materials to the rising force that was Nazi Germany.

[45] In July 1940, at the moment of crisis when Bessarabia and Northern Bukovina were ceded to the Soviet Union, Manoilescu was named foreign minister in the pro-fascist government headed by Ion Gigurtu.

The new executive was faced with eventually successful attempts by Hungary, backed by Italy and Nazi Germany, to revise its border with Romania by the Treaty of Trianon, in reality a dictate.

[5] In order to ensure less international adversity toward Romania, he also offered to cede Southern Dobruja to Bulgaria (although Germany had not included this revision in its demands toward the Romanian executive), an approach eventually leading to the Treaty of Craiova.

[47] While German Foreign Minister, Joachim von Ribbentrop, communicated the final decision, in the Gold Room of the Belvedere Palace, Manoilescu fainted, after seeing the map of the new borders, imposed by Germany and Italy, whilst the Hungarian side jubilated.

[53] In autumn 1940, he represented his country to Rome, where he attempted to persuade Italian officials to look into information about Hungarian violence in Northern Transylvania, and, in July 1942, traveled to the Independent State of Croatia to meet with Otto Franges, his collaborator on an overview of Southeast European economy.

[54] Set free in December 1945, he resumed work on his unfinished writings, and became an advocate of harvesting geothermal power in Romania (his innovations in the field were patented on the name of his son, Alexandru Manoilescu).