Wat Phra Si Sanphet was built in 1448 A.D. on the site which had served for the royal palace from 1350 to 1448 spanning the reigns of King Ramathibodi I to King Sam Phraya. King Borommatrailokanat ordered the wat built to be utilized as a monastic area.
His son, King Ramathibodi II constructed two chedi, one to house the remains of his father and the other for his brother, King Borommarachathirat III. A third chedi was built by King Borommrachnophtthangkun for the remains of King Ramathibodi II. A principal viharn (worship hall) was built in 1499 and, in 1500, King Ramathibodi II ordered the casting of a standing Buddha image 16 meters high and covered with gold. This image was called Phra Buddha Chao Si Sanphet and was the main object of veneration in the royal viharn. From that time, the remains of all royal family members were placed in small chedis built for that purpose on the site.
Wat Phra Si Sanphet was used as the royal chapel and, therefore, did not have a Sangavasa (a dwelling for monks). The wat was used for various royal ceremonies and rituals. When the Burmese sacked Ayutthaya in 1767. the gold that covered the Buddha image and other decorations was stripped away and taken by the invaders. King Rama I (1782-1809) transferred the core of Phra Buddha Chao Si Sanphet to Wat Phra Cetuphon in Bangkok.