Misawa became a puroresu fan during his junior high school years. With a recommendation of his teacher, he entered Ashikaga Institute of Technology High School, which was famous for the wrestling team, in 1978. He did not like the amateur wrestling, and one day, he visited All Japan Pro-Wrestling office. Jumbo Tsuruta suggested him to finish high school because Tsuruta himself became a pro after graduating from college. Misawa continue to wrestle in high school, and in the senior year, he won the national championship and was also ranked 5th at the 1980 World Junior Championships in the 81kg class.
He finally joined All Japan in 1981 and won the "Rookie of the Year" of the Puroresu Awards in the following year. In 1984, Shiro Koshinaka and he were sent to Mexico where they wrestled for EMLL (today's CMLL) as "Samurai Shiro" and "Kamikaze Misawa" respectively.
Misawa was brought back later in the same year as the second version of "Tiger Mask", a gimmick based on the famous comic by Ikki Kajiwara. He had the "remakes" of the feuds against the former rivals of the original Tiger Mask such as Dynamite Kid and Kuniaki Kobayashi. In 1985, he moved up to the heavyweight division, which was believed by many fans to be a promotional mistake by All Japan.
The departure of Gen'ichiro Tenryu from All Japan in 1990 gave him a big opportunity. On 1990/05/14, he unmasked himself during a match, and on 1990/06/08, he pinned Jumbo Tsuruta for the first time at Nippon Budokan. It was also around this time when he started wearing green for every match in tribute to Horst Hoffman, a legendary wrestler from Germany of whom Misawa was a fan.
In 1992, Tsuruta suffered liver problems and became inactive for a long period of time. This naturally made Misawa the top star of the organization. His tag team partner Toshiaki Kawada split from him in 1993, and the feud between the four main eventers, known as the Shitennō (Four Heavenly Kings) Puroresu, began with Misawa, Kawada, Kenta Kobashi, and Akira Taue.
On 1999/01/31, Giant Baba passed away. Misawa became the new president of All Japan, but the problems between some wrestlers and Motoko, Baba's widow, were about to come to the surface. In 2000/05, Misawa resigned as the president, around the same time Tsuruta, who had retired in the previous year, passed away. In the following month, Misawa and majority of the roster left All Japan and announced the start of a new organization.
On 2000/08/05, Misawa's new group, "Pro Wrestling NOAH", had the first card at Differ Ariake. He teamed with Taue to face Kobashi & Jun Akiyama in the main event. NOAH instantly became one of the major puroresu organizations, and Nippon TV, which had been airing All Japan shows since 1972, started a weekly program with NOAH in 2001.
However, decline of the pro-wrestling popularity in Japan also impacted NOAH. Nippon TV cancelled its weekly program on the main airwave network after broadcasting weekly puroresu shows since 1957.
On 2009/06/13, Misawa teamed with Go Shiozaki to challenge Akitoshi Saito & Bison Smith for GHC Tag Team Title at Hiroshima Green Arena. Around the 20-25min mark, Misawa received a belly-to-back suplex from Akitoshi. The referee asked Misawa whether he could move, to which he responded by saying, "ugokenai" (cannot move). He immediately lost consciousness and was taken to Hiroshima University Hospital, where his death was confirmed at 10:10pm.