The lands situated in the present-day Phitsanulok Province of Thailand have been inhabited since the Stone Age. The Neolithic inhabitants are not likely to have been ancestors of the modern Thai people who live there now. The earliest historical records relating to what is now Phitsanulok Province indicates that at a time prior to or during the 11th century, the present-day city of Phitsanulok was a small strategic settlement known as Song Khwae. During the next century, in 1188, Nakhon Thai, located near the center of the present Phitsanulok Province, was established as the capital city of the Singhanavati Kingdom, an early city-state of Thailand.

Later, during Thailand's Sukhothai Period, the city of Phitsanulok emerged as a major city in the east of the Sukhothai Kingdom, and the great temples of Wat Chula Manee, Wat Aranyik and Wat Chedi Yod Thong were constructed. In 1357, the renowned Wat Phra Sri Rattana Mahathat was erected, and the Ayutthaya Period witnessed the construction of several of the province's other chief temples. Phitsanulok served for 25 years as the capital city of the Ayutthaya Kingdom. In 1555, King Naresuan the Great was born in the city of Phitsanulok. Naresuan played a significant role in the history of Thailand, as he expanded the kingdom (then called Siam) to its greatest territorial extent, by conquering sizable portions of modern-day Burma and Cambodia. In recent times, Phitsanulok Province has become an important agricultural center, part of the Bread Basket of Thailand, providing rice and other crops to consumers in Thailand and throughout the world. Extensive agricultural development over the last hundred years or so has spawned a modern infrastructure in the urban areas of the province, bringing with it an array of modern roads, universities, hospitals and other conveniences. Over the years, the Nan River and its tributaries have played a substantial role in the history and development of the region by providing a route for transportation, fertile soil for agriculture, and water for irrigation. The river waters have also served as a route for enemy invaders, and have been the source of periodic widespread flooding throughout the province.

Prehistoric era Phitsanulok Province was inhabited during the Stone Age, as many stone axes have been found in the area indicative of the time period.Phitsanulok Thailand History However, these early hunter-gatherers are not likely to be ancestors of the Thai who now inhabit the Phitsanulok Province. The human population around Phitsanulok Province remained sparse until late in the region's history. A History of Thailand The settlement of the indigenous populations of the region began around the advent of rice agriculture during the Bronze Age, and continued through the Iron Age. Archaeologists suspect that Mon-Khmer speaking tribes spread through the region, bringing rice agriculture, metalworking, domestic animals. The main course of migration during the metal ages probably ran along the coast of Thailand, but migrants also traveled inland along the Chao Phraya to the Nan Basin and other areas, where it was relatively easier to establish settlements. The next major wave of migration into the province came not from the coast along the Chao Phraya, but rather from the mountainous areas of northern Thailand. These migrants were the Tai. Their course of immigration probably began south of the Yangzi River. As the Han Chinese spread south of the Yangzi around the sixth century BC, the ancestors of the Thai retreated into the high valleys and, over many centuries, migrated west along an arc from the Guangxi to the Brahmaputra Valley. The Thai brought rice-farming expertise to the mountainous areas of Northern Thailand, and eventually to the Nan Basin and the other lowland regions of Thailand. Some of the Nan River Mon-Khmer retreated into the hills as the Thai expansion continued, while others generally adopted dialects of the Tai languages and blended into the culture of the new settlers. The Tai language spoken in Phitsanulok (and most of modern Thailand) was heavily influenced by the Khmer culture as well, and evolved into the language we now call Thai, which is considerably different from other Tai dialects. Even after this Thai migration, the population in present-day Phitsanulok Province, other than along the banks of the Nan River was sparse. Predator animal species, as well as malaria, tropical temperatures and other hardships, kept the population from expanding far from the river, despite the region's extremely fertile soil.

Song Khwae During the 11th century the site of Phitsanulok held a small settlement called Song Khwae, meaning two rivers, which a travel feature published by Siam Commercial Bank describes as a Khmer outpost. At that time, the Nan and Khwae Noi Rivers both flowed through the city, making it a strategic gateway to northern Thailand. The urban development of Phitsanulok, which began during the trail end of the era of the Khmer Empire, was to a great extent modeled on the earlier development of the Khmer capital city of Angkor in Cambodia. In fact, Angkor Wat, the chief temple of Angkor, was a temple to the god Vishnu, whereas Song Khwae's forthcoming new name Phitsanu-lok literally means Vishnu's Heaven. These are statements about architecture and about a name, and neither is evidence of administration. Baker and Pasuk record that Angkor-influenced settlements appeared in frontier areas around the Chao Phraya plain, Sukhothai and Si Satchanalai among them, and that "some historians have read this spread as waves of conquest"; they report the reading without saying what did happen. No temple-endowment inscription of the Angkorian provincial type has been found in the plain, and the hospital and fire-house foundations of Jayavarman VII reach no further west than Prachin Buri, a statement the same authors make for that reign alone.

Singhanavati city-state In 1188 King Boromma Chayasiri of Singhanavati, a city-state centred on modern Chiang Rai, is said to have expanded it to include much of what is now Phitsanulok Province. He moved his capital to Nakhon Thai and ruled from there for a time. The early city of Nakhon Thai thereby became the second urban center of the province, and one of the few urban areas in the Nan Basin, at that time, not situated directly on the banks of the Nan River. Rather, Nakhon Thai was situated at the foothills of the Phetchabun Mountains along one of the main tributaries of the Khwae Noi River. Nakhon Thai's period as a major urban center was short lived, however, as the throne of Singhanavati moved on. The predominant city of the region throughout the Sukhothai and Ayutthaya period, as well as in modern times, would be Phitsanulok, due to the city's prime location at a major tributarial junction of the Nan River. Singhanavati survived through the Sukhothai era. The fourth successor after Boromma Chayasiri on its throne was Ramathibodi I, who became the first king of Ayutthaya in 1351.

Sukhothai period

During the Sukhothai period, Phitsanulok emerged as the major city in the east of the Sukhothai Kingdom. It is during the Sukhothai period that Theravada Buddhism was first adopted as a unifying religion throughout the kingdom (although Buddhism in general was popular throughout Southeast Asia, including Thailand, throughout the era of the Khmer Empire). As such, the Sukhothai period witnessed the construction of Wat Chula Manee and the subsequent construction of Wat Aranyik and Wat Chedi Yod Thong. The renowned Wat Phra Sri Rattana Mahathat was constructed in 1357, during the reign of King Maha Thammaradscha I of Sukhothai. Wat Phra Sri Rattana Mahathat, more commonly known as Wat Yai, is famous throughout Thailand for its golden sculpture of the Buddha called the Phra Buddha Chinnarat (). Many Thai people consider the Chinnarat, which depicts the Buddha in the posture of submission, to be the most beautiful Buddha image in Thailand. The Chinnarat is the subject of the official seal of the present-day Phitsanulok Province. While the Ayutthaya period of Thailand had already begun in 1351, Phitsanulok remained part of the Sukhothai Kingdom for some time afterward. The Sukhothai inscriptions call the town Muang Song Khwae, while the Ayutthaya annals call it Chainat until 1463. An Ayutthayan army under Borommarachathirat I took it in 1378 and received the homage of Maha Thammaracha II there. Sukhothai became a tributary state of Ayutthaya between 1365 and 1378, and in 1412, King Thammaracha IV was installed on the throne of Sukhothai by Ayutthaya. Around 1430, Thammaracha IV moved his capital to Phitsanulok, although after his death in 1438, the Sukhothai Kingdom was reduced in status to a mere province of Ayutthaya. By then, Phitsanulok can be said to have completed its gradual transition into the Ayutthaya period. Throughout the Sukhothai era, most of the land within Phitsanulok Province, aside from the city of Phitsanulok, remained sparsely populated virgin rainforest.

Ayutthaya period The Ayutthaya period was the era of chief historical importance for Phitsanulok. By this era, the city of Phitsanulok had become a major urban center, specializing in porcelain production, and in addition, Phitsanulok's grand temples built along a major strategic waterway had transformed the city into a great cultural center. In 1461, Ayutthayan King Boromma Trailokanat (1448-1488), accompanied by more than 2,000 followers attended Wat Chula Manee, where he became the first king to have been ordained as a monk, a tradition that has continued on to present-day Thailand. The Ayutthaya period was also marked with war, as the competing kingdoms of the region, now growing more and more modern and capable, were competing for both survival, and for control over larger territories. In both 1459 and 1460, the kingdom of Lanna, a buffer state between the kingdoms of Ayutthaya and Burma, attempted twice to besiege the city of Phitsanulok, although both times Phitsanulok prevailed in maintaining its sovereignty.

Phitsanulok as the Capital of Ayutthaya Kingdom Phitsanulok reached the peak of its historical import in 1463, when King Trailokanat moved the capital of the Ayutthaya kingdom to the city to strengthen the northern boundary of the kingdom. The move joined Chainat and Song Khwae inside a single wall, and Trailokanat held court there until his death in 1488. Under the Palace Law the governorship of Phitsanulok was reserved for the Royal Scion, the son of the principal queen, and a run of Suphannaphum princes went from the viceroyalty there to the throne at Ayutthaya. Joao de Barros, writing in the 1550s from traders' reports, described a northern Siamese kingdom he called Chaumua, distinct from the southern one. During Trailokanat's reign, Phitsanulok witnessed the construction of Wat Ratchaburana and Wat Nang Phaya. Around 1488, King Trailokanat's successor Boromma Racha III moved the capital of the Ayutthaya Kingdom from Phitsanulok back to Ayutthaya.

War with Burma In 1548 Khun Phirenthorathep, who had taken part in the coup that put Maha Chakkraphat on the throne, was rewarded with the title Maha Thammaracha. He received the right to issue royal command from Phitsanulok, marriage to the highest-ranking princess, the appointment of his own officials and the use of royal insignia.