Uttaradit means northern landing, as it was formerly a trade center on the Nan river.
In the Sukhothai era several city states (Mueang) subject to the king were located in the area of the modern province. Mueang Fang was in modern day Mueang Uttaradit district, Mueng Thung Yang in Laplae, and Mueang Ta Chuchok in Tron district.
During the Ayutthaya kingdom, Mueang Phichai was one of the 16 main Mueang of the Thai kingdom. In the reign of King Naresuan, the ruler of Phichai rebelled, joined by the ruler of Sawankhalok. Their revolt was suppressed and the inhabitants of both cities were forced to move south to Phitsanulok.