The earliest record of his involvement on any major project was in conjunction with his father's commission to paint elements of Oda Nobunaga's Azuchi Castle.
He received a commission from Toyotomi Hideyori to paint the ceiling of the main hall of Shōkoku-ji in Kyoto with dragons.
He took over the Kyoto Imperial Palace project, and continued to receive many illustrious commissions.
While a master of the fundamental Kanō school style, and that of his father, Mitsunobu expressed elements of his own preferences and skills in his paintings.
The emergence of his own style was not truly observed until after his father's death in 1590 and he had more independent commissions.