The community was governed as a barangay established by the Dominicans as a mission until the Spaniards gave it the status of pueblo (municipality) on May 9, 1604, making it one of the political units of the province of Cagayan. The settlement was a small in terms of population but was big in territory, which then included what would later become the provinces of Isabela, Nueva Vizcaya and Quirino till the 1850s. As a mission pueblo and with assigned encomendero (landlord) to Tuguegarao, the inhabitants (as tenants) were made to pay taxes in the form of poultry products and other food products. Resentments later flared and the people of Tuguegarao revolted in 1605, killing the encomendero. Again, the people of Tuguegarao revolted in 1718 and then 1761 under a leader named Rivera.
The first parochial building of Tuguegarao was constructed in 1604, a chapel that became the foundation of what is now the Ermita de Piedra de San Jacinto (Stone Chapel of Saint Hyacinth) dedicated to Saint Hyacinth, the patron saint of Tuguegarao. The present chapel is the latest in a process of rebuilding that started in 1724 when it was rebuilt by Fr. Bernabe de la Magdalena, O.P..
Tuguegarao became the capital of Cagayan province in 1839 when the provincial seat of power was relocated from Lal-lo. The decline of Lal-lo became the transformation of Tuguegarao as the most important town in Cagayan.
Tuguegarao was occupied by American troops on December 12, 1899. During World War II, the city and its airfield of some significance was captured by the Japanese Imperial Army on December 12, 1941 as part of the Japanese invasion of Aparri. The General Headquarters of the Philippine Commonwealth Army, Philippine Constabulary and the USAFIP-NL units was actived on 1942 to 1946 and stationed in Tuguegarao. The city and airfield were bombed by the US and Philippine regularly between January and May 1945, and attacked by Donald Blackburn's guerrilla forces in June 1945. The local recognized guerrillas helped by entering the town, Philippine Commonwealth troops under the Philippine Army and Constabulary units and USAFIP-NL military units came in early June; the town was officially liberated on June 25, 1945.
Sitio Capatan was elevated into a barrio (or barangay) Capatan of Tuguegarao on April 3, 1959 by Republic Act no. 2107.
Tuguegarao was once the only first class municipality in the province of Cagayan. It has served as the provincial capital of Cagayan since 1839 because of the notable socio-economic progress of the town. In 1975, Tuguegarao was declared as the capital and seat of the regional government of Cagayan Valley (Region II) being the region's geographic center with adequate facilities and amenities needed by such.
New barangays were formed in the 1970s that by 1981, Tuguegarao had 49 barangays, 12 of which were urban. The late 1980s saw the gradual expansion of the urban core of Tuguegarao to the outlying barangays of Ugac, Caritan and Atulayan. With the fast rising prices of real estate in the poblacion (city center), residents found it profitable to sell their properties in the poblacion and buy lots in the surrounding barangay neighborhoods, but still close to avail the amenities of the city.
By 1980, Tuguegarao had a population of 73,507. The increase in population could be attributed to various factors. One is the increasing peace and order problems in the other towns in the region driving the people to Tuguegarao, which is relatively free of the insurgency problem with the visible presence of the military and its geographic location. Another factor is the presence of the schools, whose quality of education is highly comparable to that of Metropolitan Manila. Others come because of the increase in trade and industry. The completion of the Maharlika Highway made Region II more accessible to people from other areas.
The year 1983 marked the quadricentennial celebration of the establishment of the civil government of the Province of Cagayan. In the week-long celebration held in Tuguegarao, several Philippine cabinet ministers visited the town and province.
Of very great consideration is the town's tremendous improvement in social services and infrastructure facilities since 1975. In the 1980s and 1990s, multistory buildings were constructed in the poblacion greatly changing Tuguegarao's skyline. Other changes included landscaped schools and homes, cable television, air-conditioned buses, jet flights, telegraph and telex services, door-to-door delivery services, domestic and overseas long-distance calls, luxurious social amenities and other trappings of a highly urbanized town.