Misawa was trained in professional wrestling by Dick "The Destroyer" Beyer, Shohei Baba, and Dory Funk, Jr. and made his professional debut on August 21, 1981 for All Japan Pro Wrestling.
Early in his career, Misawa wrestled as the second generation of Tiger Mask. On May 17, 1990, during a tag match against Yoshiaki Yatsu and Hiromichi Fuyuki , he told his partner and future rival, Toshiaki Kawada, to unmask him, revealing his true face. Misawa then went on to dominate All Japan Pro Wrestling throughout the 1990s, with multiple Triple Crown and AJPW World Tag Team Title reigns. His rivalries with Jumbo Tsuruta, Toshiaki Kawada, and Kenta Kobashi are legendary, with many classic matches against them. His tag-team partners included Kenta Kobashi and Jun Akiyama.
Following the death of AJPW head booker Giant Baba and disagreements with his widow Motoko Baba, Misawa split from All Japan in mid-2000, taking all but two natives (Kawada and Masanobu Fuchi) to form Pro Wrestling NOAH. In 2004, Misawa alongside his long time partner Yoshinari Ogawa returned the GHC Tag Team belts to NOAH from the New Japan Pro Wrestling combination of Yuji Nagata & Hiroshi Tanahashi. Misawa continues to wrestle a full-time schedule, leading one of Japan's top promotions.