Born into a Muslim family in Purworejo, Wilopo attended the Rechts Hogeschool in Batavia (now Jakarta), during which time he became involved in educational and nationalist groups.

After graduating, he worked as a lawyer and was active in the Indonesian nationalist movement, becoming involved in the Partindo and Gerindo political parties.

He also emerged as a leader in the Indonesian National Party (PNI) and became Minister of Economic Affairs in the Soekiman Cabinet.

After graduating from HIS, Wilopo continued his education at the Meer Uitgebreid Lager Onderwijs (MULO) in Magelang.

After studying at MULO, Wilopo continued his education at Algemene Middelbare School (AMS), in Yogyakarta.

During his stay in Yogyakarta, he enjoyed reading newsletters of the De Locomotief, Darmo Kondo, and Soeara Oemoem newspapers.

Wilopo's first government position was as the junior minister of labour during the First and Second Amir Sjarifuddin Cabinets from 3 July 1947 to 29 January 1948.

[7][8] After a brief hiatus, he became the minister of labour during the Republic of the United States of Indonesia Cabinet from 20 December 1949 to 6 September 1950.

[7][8] After completing his tenure as Minister of Trade and Industry, on 19 March 1952, Wilopo was told to choose a cabinet to lead.

Three days after giving his list to President Sukarno, on 1 April he and his cabinet took power;[9] it was essentially a coalition of necessity between the Masyumi and National parties.