He retained his ministerial position through nine different cabinets across six years, and was a member of the Indonesian delegations in the Linggadjati, Renville, and Roem–Van Roijen Agreements, as well as the Dutch–Indonesian Round Table Conference.

During his tenure as Health Minister, Leimena envisioned a plan to provide preventive healthcare in rural areas, which, despite encountering difficulties during its 1954 implementation, became the precursor of the modern Puskesmas system.

During the 30 September Movement and the ensuing political shifts, Leimena was heavily affected, his own house being attacked on the night of the incident.

[5] In 1914, Leimena moved to Cimahi, West Java; his aunt had been promoted to a principal of a school serving the children of Ambonese colonial troops stationed there.

After graduating in 1922, his aunt ruled out enrolling at a Hogere Burgerschool, and Leimena did not qualify for the technical Koningin Wilhelmina School.

[9] Leimena became a leading figure within the former, initially advocating neutrality for Jong Ambon in the background of competition between pro-independence and pro-Dutch Ambonese organizations.

[14] After graduating, Leimena first worked at Batavia's Centraal Burgerlijke Ziekenhuis (today Cipto Mangunkusumo Hospital).

[14][16] There, he was promoted to manage the education of new nurses by 1936, and he worked with a number of clinics affiliated with the hospital from the surrounding region.

In 1943, he was arrested and imprisoned by the Japanese military, likely either due to his links with socialist politician Amir Sjarifuddin or his treatment of injured Dutch soldiers after the Battle of Kalijati.

[23] According to accounts by his colleagues, Leimena initially rejected the appointment, citing his desire to work as a doctor, but he was convinced by his friend Amir Sjarifuddin, who was by then Minister of Information.

[27] Beyond his cabinet position, Leimena agreed to chair the Pemuda Indonesia Maluku (PIM), a pro-Indonesian Ambonese organization formed by Johannes Latuharhary.

[34] When the South Maluku Republic (RMS) was declared in Ambon in the aftermath of the Dutch recognition of Indonesian sovereignty, Leimena was dispatched to Ambon to lead the Indonesian government's initial negotiating party ("Leimena mission") with RMS leaders aboard the corvette Hang Tuah.

[36] Leimena had initially intended to travel to Ambon aboard a KNIL aircraft, but this was overridden by the Defense Minister at that time.

[48] Under a fellowship from the World Health Organization, Leimena travelled to Europe in 1953, where he observed the healthcare systems of Norway, the United Kingdom (NHS), and Yugoslavia.

He also went to Egypt, India and Singapore, where he also attended lectures and discussions in addition to observing existing health services.

The Norwegian health system, which envisioned raising the standards of living through the improvement of nutrition and working conditions, left an impression on Leimena.

Leimena, who stayed in Geneva, apparently intended to resign and reportedly said that he felt like "a fisherman who has caught something and is told to throw it back into the water".

Other members of the committee were Sukarno, Mohammad Hatta, Djuanda Kartawidjaja, Abdul Haris Nasution, Hamengkubuwono IX, and Azis Saleh.

[62][63] In November 1963, following the unexpected death of Djuanda, a presidium was appointed by Sukarno to manage the cabinet, consisting of Leimena, Subandrio, and Chaerul Saleh.

[64] During the whole of the Guided Democracy period, Leimena remained a close ally of Sukarno, being skilled with handling the political elite, though he lacked the ability to organize large-scale popular support.

[70] In the immediate aftermath of the incident, still on the morning of 1 October, Leimena was summoned by Sukarno to Halim Perdanakusuma airforce Airbase,[71] where he had gone to speak with the coup leaders.

[73] Leimena was named by the coup plotters as part of an "Indonesian Revolution Council" (nearly half of which was sitting government officials) on the afternoon of 1 October.

Later in the afternoon, Leimena joined Sukarno and two other Deputy Prime Ministers (Subandrio and Chaerul Saleh) in meeting with Army generals Amirmachmud, Mohammad Jusuf and Basuki Rahmat at the Bogor Palace.

[84] During the New Order, Suharto reportedly intended to retain Leimena as a minister, but the latter politely refused the position by going through Hamengkubuwono IX.

[89] This opposition to both positions partly led to Leimena's strong affinity toward Sukarno, who leaned toward a Pancasila-based state.

[60] Despite this view, Leimena found much common ground with some of the more socialist-leaning Islamic Masyumi leaders such as Mohammad Natsir and Sjafruddin Prawiranegara.

[90] Leimena gave two addresses to meetings of the DGI in 1950 and 1964, where he promoted the idea where the interests and aims of the church are parallel with that of the country.

[93] Leimena married his wife, Wijarsih Prawiradilaga, an ethnic Javanese Muslim woman, during his time working as a doctor in Bandung.

[97] In his autobiography, Sukarno noted how Leimena, while on diplomatic missions during the Indonesian Revolution, lacked formal clothes and had to borrow sets of a suit and tie from colleagues.

[22] In 2010, 33 years after his death, Leimena was awarded the title of National Hero of Indonesia by President Susilo Bambang Yudhoyono.