During the Ayutthaya-Lanna War, King Trailokanat moved his residence to Song Khwae in 1464 and renamed the city "Phitsanulok" (from Sanskrit Vishnu and Loka "world").

In the sixteenth century, Phitsanulok was the seat of Uparaja or heir presumptive to Ayutthaya throne who took residence in the Chantana Palace on the west bank.

King Thammaracha, now reigned at Ayutthaya, appointed his son Prince Naresuan as the Uparaja of Phitsanulok in 1570.

In 1584, Prince Naresuan ordered the evacuation of all cities in the Sukhothai region including Phitsanulok down south in preparations against Burmese invasions.

Phitsanulok was abandoned until it was later restored in 1593 not as a Uparaja seat but as a Muang Ek or first-level city held by a governor, becoming the center of Siamese administrations in northern regions.

The Burmese invaded again in 1785 and Phitsanulok was abandoned temporarily because the manpower shortage left the city defenseless.

The Phra Buddha Chinnasri image was moved to Wat Baworn Niwet in Bangkok in 1829.

Phitsanulok covers some 777 square kilometres and borders Uttaradit and Laos to the north, and Loei and Phetchabun to the northeast.

The monsoon season runs from May through October, with heavy rain and somewhat cooler temperatures during the day, although nights remain warm.

The administration of Phitsanulok City Municipality is responsible for an area that covers approximately 18.26 km2 (7.05 sq mi) and consists of only tambon Nai Mueang with 62,584 people and 37,507 households.

The mayor, or the highest executive, is directly elected by the eligible voters in the municipal area.

The people of Phitsanulok are predominantly Theravada Buddhists (as are 95% of the Thai population as a whole), with a small Christian community and a few Muslim families.

Now in Tha Pho, near the city of Phitsanulok, the university was named after King Naresuan the Great, and the campus features a large statue of him.

Yanyon tour operates its own private bus station (Sua Thim) with only a busline to Bangkok.

In the city center, Phitsanulok railway station mainly receives intercity trains on the Northern Line, operated by State Railway of Thailand, more than a dozen trains running in each direction each day.

The beautiful mother-of-pearl inlaid doors were built in 1756 by order of King Boromakot of Ayutthaya.

The Buddha Chinnarat National Museum, on the temple grounds, houses a sizeable collection of Sukhothai period art.