During World War II, while practicing medicine, he worked with anti-Japanese resistance forces.

Subandrio was the main architect of Indonesia's left-wing foreign policy during this period, including the alliance with the People's Republic of China and the policy of "Confrontation" with Malaysia, which created great hostility between Indonesia and the Western powers, particularly the United States and the United Kingdom.

He was heavily involved in the Sunda Straits Crisis of 1964 when the British aircraft carrier HMS Victorious passed through Indonesian waters without proper approval.

Subandrio was sentenced to death by the Extraordinary Military Court on charges of being involved in the "30 September Movement," although there was no real evidence that Subandrio knew of the plot in advance or played any part in it (he was in Sumatra at the time[4]).

This sentence was afterward reduced to life imprisonment upon the request of the British government on behalf of Queen Elizabeth, as it was remembered that Subandrio was Indonesia's first envoy to the U.K.