Trujillo was settled on a granite batholith during the Prehistoric times. In Roman times the town was known as Turgalium and became a prefecture stipendiary of the Lusitanian capital, Emerita Augusta. He was later populated by barbarian tribes (mainly Visigoths) although the prevalence of the population would still be Hispans. Then the Muslims came, becoming one of the main towns in the region of influence governed from Madrid (which was even formed one of the Taifa kingdoms). After five centuries of Muslim occupation, in 1186, while Alfonso VII of Castilla was the king, several missions tried to reconquer the town, but they failed. It was 25 January 1232, in times of King Ferdinand III when, according to the local legend, the Virgen de la Victoria appeared to Christian troops at the Arco del Triunfo before managing to retake the city, defeating the Arabs who were in it, anticipating the outcome of the battle.

King Juan II of Castilla gave the town the title of city in 1430. Later it had a Jewish quarter located outside of the powerful medieval walls. Trujillo, with the growth of the population was gradually extended beyond the walls.

Then some Trujillanos went to America to discover new places. When they come back, the built majestic palaces near the Plaza Mayor and surrounds, most of them can be visited today.

In 1834 the city became the official headquarters of the Judicial District of Trujillo. In the census of 1842 it had 110 households and 6026 residents.