Honda Yasushige served as a bushō and daimyō from the Sengoku to early Edo periods.  He was the first lord of the Mikawa-Okazaki domain.  As a daimyō, he became the first head of the Honda Bungo-no-kami family.

Yasushige was born as the son of Honda Hirotaka.

In 1562, Yasushige attended his coming-of-age ceremony and received from Tokugawa Ieyasu one of the characters in his name.  In 1569, he had his first experience in battle during an assault on Kakegawa Castle.  Yasushige served in the Battle of Anegawa in 1570 and the Battle of Nagashino in 1575.  In particular, at the Battle of Tobinosuyama in the course of the Battle of Nagashino, he fought valiantly despite being shot in the left thigh by the Takeda army.  The bullet remained in his leg for the remainder of his life.

In 1577, Yasushige inherited the headship of the clan.  After the Conquest of Odawara, when Ieyasu was transferred to the Kantō, Yasushige was moved from Tahara Castle in Mikawa Province to the Kōzuke-Shiroi domain and granted a fief of 20,000 koku.  After the Battle of Sekigahara, in 1601, he became the first lord of the Mikawa-Okazaki domain with a fief of 50,000 koku.

On 3/22 of Keichō 16 (1611), Yasushige died at the age of fifty-eight.  He was succeeded by his eldest son, Honda Yasunori, who became a daimyō and served as the second head of the Mikawa-Okazaki domain.