In 1858, the U.S. Army chose San Antonio as the location for a permanent arsenal, an Army facility including buildings for storage of weapons and gunpowder. Previously located in rented buildings, including the Alamo, a site was purchased south of downtown on the San Antonio River.

The property included the old home of Dr. James M. Devine, and it was used to house the Arsenal's highest ranking officer. New Army buildings were constructed around it and the facility, though incomplete, was occupied by Confederate troops during the Civil War. The complex was finished after the war and in 1883, a new Commander's House was built on the Devine House site. When the roof was replaced and a wing added in about 1886, the house took on the appearance we see today.

Near the house, a small outbuilding pre-dates 1857 and is one of San Antonio's oldest residential buildings. When the Commander's House was no longer used by the United States government, it was declared surplus property and deeded to the City of San Antonio. The building has served as a popular Senior Citizen's Center since 1978.