The area around Misawa has been occupied since prehistoric times, and was a major population center for the Emishi people. Numerous Jomon period remains have been discovered within the borders of Misawa, including within the borders of Misawa Air Base. The area was nominally under control of the Northern Fujiwara in the Heian period, and became part of the holdings granted to the Nanbu clan after the defeat of the North Fujiwara by Minamoto Yoritomo in the Kamakura period. The Nanbu established numerous horse ranches, accompanied by numbered fortified settlements. During the Edo period, the area was part of Morioka Domain. After the Meiji Restoration, the area was settled by many dispossessed ex-samurai from former Aizu Domain.
Per the reform of 1889, Misawa Village was created within Kamikita District through the merger of Misawa and Tengamori hamlets. The area was devastated by a tsunami in March 1896. In 1931, in the first successful nonstop transpacific flight, Clyde Pangborn and Hugh Herndon, in the airplane Miss Veedol, took off from Misawa's Sabishiro Beach and landed in present-day East Wenatchee, Washington. Coastal areas of Misawa were again devastated by a tsunami in March 1933. An Imperial Japanese Navy Air Service base was established in 1941, and nearby Lake Ogawara was reportedly one of the lakes used by the Imperial Japanese Navy to practice for the attack on Pearl Harbor due to its shallow depth. The base was heavy bombed by the United States Navy in 1945, and subsequently occupied by the United States after the surrender of Japan at the end of World War II.
On February 11, 1948, the town of Omisawa was founded through the merger of Misawa village with portions of Rokunohe, Shimoda and Uranodate villages. Misawa Airport was opened on January 11, 1952, with Japan Airlines providing scheduled services to Haneda Airport in Tokyo and Chitose Airport in Hokkaid?. The town was elevated to city status on September 1, 1958. Misawa Airport was
