The street is named after Enrique Mendiola, the pedagogue, author of textbooks, educator and member of the first Board of Regents of the University of the Philippines.

As a street leading to Malacañang Palace, the President of the Philippines' official residence, it has been a convergence area of numerous and sometimes bloody demonstrations.

[4][5] On January 22, 1987, crowd control troops opened fire on a protest rally of about 10,000 peasant farmers demanding "genuine" land reform from then-President Corazon Aquino.

[6][7] On May 1, 2001, supporters of former President Joseph Estrada, angered by his arrest following his ouster from power earlier that year, marched to Mendiola Street after staging demonstrations outside the EDSA Shrine.

As a result of the looting of stores and shops and the burning of several government and private vehicles by the protesters, damage to and loss of property along Mendiola Street and areas within the vicinity of Malacañang Palace was estimated to be millions of pesos.