Iskaq was one of the earliest native Indonesian advocates during the Dutch colonial period, founding multiple law offices across the country.

During the Indonesian National Revolution, Iskaq briefly served as the Resident of Banyumas and Mayor of Surakarta, before becoming Minister of Home Affairs during the Sukiman Cabinet.

He returned to government office as Minister of Economic Affairs in the First Ali Sastroamidjojo Cabinet, where he became entangled in a graft scandal.

[7] Iskaq co-founded the Indonesian National Party (PNI) in 1927, and in its initial provisional leadership he was appointed as secretary/treasurer while future President Sukarno served as chairman.

[8] In 1929, along with Sukarno and a few others, Iskaq was arrested due to involvement in PNI – and then shortly after released, under the conditions that he not return to Batavia or Bandung.

[11] During the Japanese occupation of the Dutch East Indies, Iskaq was made the assistant resident of Banyumas,[12][13] and was appointed into the Central Advisory Council, a representative body.

[14] Following the surrender of Japan and the proclamation of Indonesian Independence, Iskaq became the resident, and facilitated negotiations of the disarming of 450 Japanese troops in Banyumas - hence giving their weapons to the nationalist units under the command of General Sudirman.

As part of this office, Iskaq and Sudiro organized the region, previously under the Surakarta Sunanate and Mangkunegaran administration during the colonial period, into a regular Residency.

[17][18][19] Iskaq later took part in the Renville Agreement, a meeting between Indonesian and Dutch leaders to demarcate boundaries between territories controlled by the two sides.

His decision to appoint Sanusi Hardjadinata, a member of the PNI, to the Masyumi stronghold of West Java, and Sudiro, an ethnic-Javanese for Sulawesi, caused political controversy.

While the decree was later revoked, it still saw some enforcement, and led to the growth of "Ali Baba" partnerships with an indigenous license-holder and a Chinese Indonesian trader, and there was widespread corruption in the licensing process.

[28][31] Additionally, Iskaq also replaced many high-ranking officials of state-owned banks and government bodies under the ministry with PNI members.

While a number of officials at the import licenses office were arrested, Iskaq was only investigated and not prosecuted upon his return to Indonesia in April 1956.

[3][37] In late 1965, following an attempted coup, internal disputes within PNI arose from the suspension of members such as Osa Maliki, Hadisubeno Sosrowerdojo and Hardi.

During the congress, many delegations who supported Ali's leadership were restricted or arrested, with the military being friendly to Osa Maliki's faction of the party.

Iskaq refused to participate in the new party,[6] instead founding the "Marhaenism Foundation" in 1980 and the "Indonesian National Movement" in 1982 in an attempt to organize former PNI members.