It is believed that the history of the province dates back to over 25,999 years ago with the Stone Age race of dark-skinned, kinky-haired pigmies whose descendants, the nomadic Aetas (Negritos), can still be found roaming the mountains and forest of eastern Isabela today. The Indonesians arrived 5,000 years ago, followed by three waves of Malays between 200 BC and 1500 AD. These pagan ancestors of the Ibanags, Gaddangs, Yogads, Kalingas, and other original tribes of the valley built a civilization based on corn agriculture and organized around the fundamental political unit, the barangay.
The Spaniards arrived in the late 16th and 17th centuries and introduced Christianity, the encomienda (forerunner of the municipality) system, and the tobacco monopoly. Spanish rule was extremely oppressive so the natives rose in revolt on several occasions, most notably in the 18th century under the leadership of Dabo and Marayag
According to Fr. Ambrocio Manaligod, STD, from 1851, the Spanish conquistadors established the “Ciudad de Nueva Segovia” in what is called Lallo today. Up to 1839, the entire Cagayan Valley was one large province which the Spaniards called “La Provincia del Valle de Cagayan.” Out of this vast territory, two new provinces were created in 1839. One retained the old name “Cagayan” which comprised all towns from Aparri to Tumauini. Its capital transferred from Lallo to Tuguegarao. The one bearing the name “Nueva Vizcaya” was composed of all towns from Ilagan to the Caraballo del Sur including Catalangan and Palanan, with Camarag (now Echague) as its capital.
A Royal Decree was created in May 1, 1856 creating “Isabela de Luzon” to distinguish it from other Isabelas in the Philippines. It comprised the town of Carig (now Santiago City), Camarag (now Echague), Angadanan (now Alicia), Cauayan, Calanusian (now Reina Mercedes), Gamu, and Ilagan, all detached from Nueva Vizcaya; while Tumauini and Cabagan were taken from the province of Cagayan. It was placed under the jurisdiction of a governor with the capital seat at Ilagan, where it remains at the present.
A new wave of immigration began in the late 19th and 20th centuries with the arrival of the Ilocanos who came in large numbers. They now constitute the largest group in the province. Other ethnic groups followed and Isabela became the “melting pot of the north.”
Although the province did not play a major role in the revolt against Spain, it was in Palanan where the final pages of the Philippine revolution were written when the American forces led by General Frederick Funston captured General Emilio Aguinaldo on March 23, 1901.