This railroad depot was built by the Flint & Pere Marquette railroad when the railroad came to Sanford in 1870. It was originally located in town near the present day site of the Sanford trail head of the Pere Marquette rails to trails.
It is the oldest building on the museum grounds and served the village until 1947. Eventually the depot was acquired by private individuals and moved to the corner of old US 10 and West River Road where it sat for a number of years in disrepair. Steve Hyer donated the depot to the Sanford Historical Society in 1984 and it was moved to the museum grounds that same year. The depot was repaired and restored over a period of several years. The roof was repaired and the floor almost entirely rebuilt.
The back of the depot was used for receiving and shipping various items via the railroad. The front of the depot had an office for the station master, who was the head man of the depot, and a waiting room for the passengers.