Ang paaralang ito ay naitatag ng mga Kastila sa utos ng Ayuntamiento de Manila sa daang Victoria, Intramuros noong 1892. Pinangalanang "Escuela Municipal de Manila". Dito rin itinatag ng mga Amerikano ang kauna-unahang paaralang bayan sa ilalim ng kanilang pamamahala noong Hunyo 11,1906 sa pangalang "Manila High School". Naging "Manila South" at muling pinagalanang "Manila High School". Ito ang una at tanging mataas ng paaralang bayan isinunod sa pangalan ng Punong Lungsod ng bansa. Ang unang gusali ay nagiba noong ikalawang Digmaang Pandaigdig. and kasalukuyang guasling ito ay pinasinayaan noong Pebrero 26,1967. Kabiling sa mabubunying nagtapos sa paaralang ito ang tatlong naging pangulo ng Pilipinas na sina Jose P. Laurel, Manuel A. Roxas at Elpidio Quirino, ang bantog na Heneral Carlos P. Romulo ng Minsitri ng ugnayang panlabas at kauna-unahang pangulo ng nagkakaisang bansa (UNO), at marami pang ibang matagumpay na pinuno sa larangan ng Aghan, Edukasyon, Pangangalakal at Lingkod ng Bayan.
Translated, the marker reads:
By the command of the Ayuntamiento de Manila, this school was established on Victoria Street, Intramuros in 1892. Named as "Escuela Municipal de Manila". This is also where the Americans established their first school under their government on June 11, 1906 under the name of "Manila High School". Renamed Manila South and again to Manila High School. This is the first and only school that was named after the capital of the country. First building was destroyed during World War II. The current building was built on February 26, 1967. Notable graduates from this school include three presidents of the Philippines, Jose P. Laurel, Manuel A. Roxas, and Elpidio Quirino, the famous General Carlos P. Romulo of the Minister of Foreign Affairs, the first Filipino President of the United Nations General Assembly, and others who became successful in the fields of Science, Education, Trade and Serving the country.