The Tupelo Cotton Mills began operations in 1901 on the south side of Tupelo adjacent to the tracks of the Mobile and Ohio Railroad (today the Burlington Northern Santa Fe Railway Company [BNSF]) where they intersect with the north-south Kansas City Southern Railway line. At S. Broadway and Elliott streets the older north section of the main brick building has plentiful windows and a tall square tower. An extension to the south (1919) has a poured-in-place concrete frame. A brick powerhouse with smokestack stands to the east. The Tupelo Garment Company Building, located west of the cotton mill, north of Blue Bell Alley, and south of the BNSF tracks, was built in 1929. Two and three stories tall, it has relentless rows of tall brick piers alternating with steel windows and brick spandrels.
Cotton Mill owners constructed housing for mill workers along S. Broadway, Maple, and S. Green streets. Most of the houses date to 1901–1909 and 1919–1924. The most common type is an L-front cottage, but there are also shotgun houses and some bungalows, as well as several Queen Anne cottages, which may predate the village. After a workers’ strike in 1937, the cotton mill owners closed their production facilities and sold their housing stock.
West of the mills at the intersection of S. Church Street and the BNSF tracks stands the former Carnation Milk Plant (1927; closed in 1965). Built at the height of the dairy industry in the area, it produced condensed milk. The long, variable-height production building has concrete walls, an internal steel frame, and a tall concrete smokestack.