Mitsubuchi Mitsuyuki served as a bushō during the Azuchi-Momoyama period for the Hosokawa family and as a hatamoto, or direct retainer of the shōgun, during the early Edo period.  He was born as the second son of Mitsubuchi Fujihide.

In 1574, Fujihide incurred the wrath of Oda Nobunaga and was ousted.  Later that year, Fujihide and his older brother, Akihide, killed themselves at Sakamato Castle, the base of Akechi Mitsuhide where they were being held.  This marked the end of the Mitsubuchi clan, a branch of the Ashikaga shōgun family originating from the Seiwa-Genji family.  The Mitsubuchi were a renowned family in the hōkōshū, a military organ under the direct control of the Muromachi bakufu.  At the time of his father’s demise, Mitsuyuki was still a young child, so his life was spared.  He was raised by his uncle, Hosokawa Yūsai (a renowned cultural figure and master of waka), and became a retainer of the Hosokawa family.

In 1600, at the Siege of Tanabe Castle in advance of the Battle of Sekigahara, Mitsuyuki aided Yūsai who was holed-up in the castle and resisted valiantly.  His acts of valor were highly praised by Tokugawa Ieyasu.  On 6/22 of Keichō 9 (1604), Mitsuyuki was invested with the title of Junior Fifth Rank (Lower) and Governor of Hōki.  In the tenth month of 1609, he was granted 1,000 koku in the Kanzaki District of Ōmi Province.  In the Edo period, Mitsuyuki became a hatamoto, or direct retainer of the Edo bakufu, reviving the Mitsubuchi clan.

Mitsuyuki died in 1623 and was succeeded by his son, Mitsubuchi Fujitoshi.