19th-century Siamese historian and statesman Damrong Rajanubhab speculated that the city was founded under the name Suvarnapurī around 1350, around the time when nearby U Thong was plagued by an epidemic.

U Thong's ancient name was Suphannaphum or Suvarnabhumi (literally: the origin or birthplace of gold), which was probably abandoned when the water shortage epidemic raged and Suvarnapurī was founded along the Tha Chin River.

Ramathibodi appointed his brother-in-law Khunluang Pha Ngua as governor of Suvarnapurī, who gave the city its present name Suphanburi and who would become king of Ayutthaya in 1370 with the name Borommarachathirat I.

The battle was in progress, when the Siamese king Naresuan challenged the heir to the throne of the Toungoo dynasty to a duel on the back of elephants to decide the fate of the clash.

Within minutes Naresuan killed his rival, the Burmese troops withdrew and Ayutthaya thus gained independence after 29 years of vassalage at Pegu's court.

Suphanburi underwent major changes in the years between the 20th and 21st centuries at the behest of Banharn Silpa-Archa, a wealthy entrepreneur native of the city who was prime minister of Thailand between 1995 and 1996.