He subsequently served as a metsuke, and played an important role in the persecution and eradication of Kirishitan religion from Japan.
After the suppression of the Shimabara Rebellion, he was raised to the status of a 10,000 koku daimyō and assigned the newly formed Takaoka Domain.
However, Masashige never actually visited his domains, dividing his time between Edo and Nagasaki on official duties, and his revenues were increased to 13,000 koku in 1644.
His son, Inoue Masakiyo likewise spent his time in Edo, but giving up 1500 koku in revenue to his younger his brothers.
He was appointed domain governor under the new administration, until the abolition of the han system in July 1871 and subsequently served in the police forces of the new government and became a viscount under the kazoku peerage.