The post office in the Appanoose County town of Moulton was established in March 1868 with Jacob Neal appointed as the first postmaster. For nearly a century, the post office has been located in the eastern part of a two-story pressed brick building located along Main Street in downtown Moulton. The building was constructed in 1902 at a cost of $14,000 for use as the State Savings Bank, which occupied the west wing of the facility. After the bank closed its doors during the Great Depression, the building was sold at public auction and has since seen various occupants in portions previously occupied by the bank, including dentists, doctors and lawyers.

The building caught on fire in December 1940, but the post office escaped mostly unscathed. Nonetheless, it was relocated to the west section of the building while repairs were made. The full-time office is one of 9 active Post Offices in Appanoose County.