Tjokroaminoto's involvement in politics and social reform began when he became a member of the Budi Utomo, an early Indonesian nationalist organization. However, it was his leadership in the Sarekat Islam (Islamic Association), founded in 1911, that catapulted him to national prominence. The Sarekat Islam aimed to improve the socio-economic conditions of Indonesian Muslims and challenge Dutch colonial rule through non-violent means.

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Throughout his life, Tjokroaminoto faced numerous challenges and threats from the Dutch colonial authorities, who saw him as a threat to their control. Despite these obstacles, he remained committed to his ideals, inspiring a generation of Indonesian nationalists, including Sukarno, who would later become the country's first president.