This place was used during the Spanish occupation and the migration of the neighboring towns to settle in the more fertile plains of Ormoc. Much of the settler in the town were the Malayans. These people had a constant trading with the Chinese, Javans and Indonesians. Their living, however, was always threatened by the attack of the Moro pirates. It is said that the people in Ormoc developed a warning system communication through people manning watch towers to inform and warn the people of the coming of these pirates.
Jesuit missionaries arrived in Leyte. On May 1507, a mission in Ormoc was established by these missionaries. That year, the locals were converted to Christianity. Their years of peace was shortly felt when in year 1634, a ruler of Sulu by the name of Raja Bungsu captured 300 natives form Ormoc after the invasion of the notorious pirates in the town. The towns of Sogod, Kabalian, Inopacan and Baybay were also invaded and plundered. More locals of Ormoc still fought this Raja and his men but because they were outnumbered, they were massacred up to the last man.
Ormoc is a hotbed of revolutionaries seeking independence from Spanish rule. The revolutionary leader Faustino Alben inspired locals to join the Pulahan Movement.
After the Japanese Occupation and a rule of Second Philippine Republic. Ormoc is a garrison of small divisions of the Imperial Japanese Army. With the Allies near the City. Japan begin to reinforce the city and the Battle of Ormoc Bay begins. The city is liberated afterwards.
Ormoc became a city by virtue of Republic Act No. 179 on October 20, 1947, becoming the fifteenth city in the Philippines and the first in the Eastern Visayas region.
On the morning of November 5, 1991, the Ormoc region was inundated by Tropical Storm Uring. The city government recorded 4,922 deaths, 3,000 missing persons, 14,000 destroyed houses and more than P600 million worth of damaged property. None of the 3,000 missing persons were ever found and are now presumed dead. Illegal logging and kaingin (slash-and-burn farming) were blamed as the reasons of the flood. Heavy rainfall caused water to collect upstream the Anilao and Malbasag rivers until it poured to the lowlands in Ormoc, particularly District 26, also known as Isla Verde. On November 5, 2011, a monument by national artist Francis Cinco commemorating the 20th anniversary of the event was inaugurated. It sits on top of the mass grave at the Ormoc City Public Cemetery where an estimated 4,900 victims are buried. The sculpture, entitled "Gift of Life", is an abstract depicting a life taken to heaven.
On November 7, 2013, Typhoon Haiyan, one of the most powerful tropical cyclones ever recorded, made a landfall in the Philippines. While it killed far fewer people as Tropical Storm Uring, it left widespread devastation to the city with destruction and damages in 90% of its structures.
On January 19, 2021, the City Council enacted Ordinance 52 Series of 2021 to merge the numbered barangays (all in Poblacion) and renaming them: