By 1902, he and his brother Ricardo, working on the anti-Díaz broadsheet El Hijo del Ahuizote, were arrested and incarcerated in the military prison at Santiago Tlatelolco.

Upon their release from prison in January 1903, the brothers returned to publishing El Hijo del Ahuizote and, on 5 February of that year, Enrique Flores Magón drew a banner declaring "The Constitution is Dead", which they hung in front of its offices.

On 2 April 1903, they and other liberals stormed a pro-Díaz demonstration and succeeded in turning it into an anti-Díaz event, calling for the dictator's death.

Enrique lived in several cities around the U.S. and Canada, concealing his identity, constantly changing address, and frequently losing contact with Ricardo.

He recommenced publication in the United States of the newspaper Regeneración, which the brothers had founded in 1900, and organized a clandestine network for its distribution in Mexico.