Born in Mino province--now Gifu prefecture--as a descendant of the shugo Toki clan, Mitsuhide began serving Nobunaga after the latter's conquest of Mino province in 1566 and received Sakamoto (in Omi, 100,000 koku) in 1571. Although Nobunaga rarely put too much trust in his retainers, he particularly trusted Katsuie Shibata, Hideyoshi Hashiba, and Mitsuhide Akechi. After Mitsuhide received Sakamoto he moved to pacify the Tamba region by defeating several clans such as the Isshiki of Tango.
In 1579 he captured Yakami Castle from Hatano Hideharu by promising Hideharu peace terms. This accomplished Mitsuhide's goal, although Nobunaga betrayed the peace agreement and had Hideharu executed. This displeased the Hatano family, and a short while later several of Hideharu's retainers murdered Akechi Mitsuhide's mother. The situation was fueled through several public insults Nobunaga had directed at Mitsuhide that even drew the attention of some Western observers. Mitsuhide blamed Nobunaga for his mother's death and at the Incident at Honnōji on June 21, 1582 (Japanese: 6th month 2nd day) exacted his revenge.
He has been credited with killing Oda Nobunaga; while Mitsuhide did not execute Nobunaga personally, he did force him to commit seppuku for his betrayal and subsequent murder of Mitsuhide's mother. When they found out about the assassination, both Hideyoshi and Tokugawa Ieyasu rushed to be the first to avenge Nobunaga and take his place. Hideyoshi got to Mitsuhide first, and Mitsuhide's allies such as Hosokawa Fujitaka, who was related to Mitsuhide through a marriage, betrayed him. Mitsuhide survived for 14 days until he was defeated by Hideyoshi at the Battle of Yamazaki. Mitsuhide is rumored to have been killed by a peasant warrior with a bamboo spear by the name of Nakamura; however, there were also rumors that he was not killed, but rather started a new life as a priest called Tenkai.
The Akechi family was able to trace their heritage to the Toki clan and from there to the Minamoto clan. It is noted that Minamoto Yoritomo brought the destruction of the Taira clan the same way Mitsuhide brought an end to Nobunaga, who traces his ancestry to the Taira. The sword of Mitsuhide has Tensho style, in fact, the Tensho Koshirae Iaito was first designed to be a replica of Akechi Mitsuhide's own sword.