Many famous people claim Ōshū as their home, including Los Angeles Dodgers baseball player Shohei Ohtani and Ichiro Ozawa, the long-time leader of the Democratic Party of Japan.

The area of present-day Ōshū was part of ancient Mutsu Province, and has been settled since at least the Japanese Paleolithic period.

By the Nara period, Japanese hunters, trappers, settlers and itinerant missionaries were visiting and settling in this area, and coming into contact with the native Emishi people.

In 729, Kokuseki-ji temple claims to have been established by the Buddhist priest Gyōki in a mountainous area to the east of the Kitakami River in what is now Mizusawa.

In June 787 Emishi cavalry led by Aterui and More surprised and routed a larger force of Japanese infantry in the Battle of Subuse (located in what is now part of Mizusawa).

Early in the 11th century Abe no Yoritoki refused to pay taxes to the central government, led raiding parties south of the Koromo River, and generally ruled as an independent monarch.

It is the third head temple of the Sōtō sect of Zen Buddhism and boasts the largest thatched roof in Japan.

Following the Battle of Sekigahara, the Tokugawa shogunate confirmed the area was part of Sendai Domain under Date Masamune.

Foreign missionaries continued to visit the area in secret until December 1623 when the Jesuit Padre Diogo de Carvalho from Portugal was captured on the upper reaches of the Isawa River, sent to Sendai and forced to stand in the frozen Hirose River until he died in the early hours of what was then New Year's Day, namely February 19, 1624.

Ōshū has a mayor-council form of government with a directly elected mayor and a unicameral city legislature of 28 members.

In terms of national politics, the city is part of Iwate 3rd district of the lower house of the Diet of Japan.