In 1889 Muñoz Rivera founded the newspaper La Democracia, which crusaded for Puerto Rican self-government. He became a leader of the autonomist parties, and in 1897 he was instrumental in obtaining Puerto Rico's charter of home rule from Spain. He soon became secretary of state and later president of the first autonomist cabinet. He resigned in 1899 after the United States put an end to Puerto Rico's short-lived home rule.

Spending the remainder of his life primarily in the United States, Muñoz Rivera continually advocated the cause of Puerto Rico's autonomy. In 1910 he became Puerto Rico's resident commissioner in Washington, D.C. Muñoz Rivera's son Luis Muñoz Marín (Muñoz Marín, Luis) was governor of Puerto Rico from 1949 to 1965.