He studied at San Juan de Letran and University of Santo Tomas. He contracted polio while still a student. Notwithstanding his disability, he joined Masonry, the La Liga Filipina, and, when it was dissolved following Dr. Jose P. Rizal’s deportation to Dapitan, joined the Katipunan. He wrote in Spanish the Katipunan’s by-laws which Emilio Jacinto translated to Tagalog for the benefit of the Katipuneros.

Spared by the colonial authorities because of his disability, he was placed under house arrest after the revolution broke out in August, 1896. In August, 1898, he wrote a manifesto addressed to the leaders of the Philippine Revolution where he predicted the Americans would annex the Philippines and he exhorted the leaders to prepare for such eventuality and fight for their country’s independence. Because of this manifesto, he attracted President Emilio F. Aguinaldo’s interest. On recommendation of Don Felipe Agoncillo, President Aguinaldo took Mabini as his adviser on state matters. Mabini wrote most of Aguinaldo’s decrees, organizing local and national government’s especially his June 18 and 28, 1898, decrees. Mabini also served as President of the Council of Secretaries and Secretary of Foreign Affairs. It was Mabini’s idea to send Filipino representatives abroad to secure foreign recognition and support for the Filipino government. Thus, the Americans called him "El Cerebro y Nervio del Gobierno Filipino (the Cerebrum and Medulla Onlongata of the Filipino government)."

Captured and kept prisoner by the Americans, he was deported to Guam when he published his article "El Simil de Alejandro" in the newspaper El Liberal. The article criticized America’s role in the Philippines as contrary to the God-given night of the Filipino people to govern themselves. He returned to Manila on February 26, 1903.

Mabini took the oath of allegiance because he did not want to die in a foreign land – a fate that he considered worse than a death sentence. The American authorities offered him a various high positions but he declined and the retired to his residence in Nagtahan, Manila. He died of cholera on May 13, 1903.

His countrymen and the colonial authorities considered his untimely death a big loss to the Filipino people and their struggle for self-rule. The high praises heaped on him by friends and foes testify to Mabini’s integrity and sterling character. Wenceslao Retana, former enemy, gave Mabini the highest homage. Retana called Mabini the "Robespierre-Mirabean-Conthon of the Philippines." The Philippines and the Filipino people are fortunate for having begotten a great man like Mabini.