The history of Tupelo begins in an area known to early settlers as Gum Pond. This corner owed its name to the abundance of tupelo (nyssa) trees that grew densely around the water bodies on lands inhabited by the Chickasaw people before the arrival of Europeans. A turning point in the fate of the future city was the laying of the Mobile and Ohio Railroad tracks in 1859. The railway station quickly became a centre of attraction, and in 1870, Tupelo was officially incorporated, replacing the older neighbouring settlement of Harrisburg.
The city's favourable geographical location in the northeast of Mississippi played a key role in its formation. Wooded hills provided access to valuable timber, whilst fertile soils promoted the development of agriculture. The railway became the main vital artery, allowing trade flows from surrounding villages to be redirected straight into the growing city, providing it with an advantage over its neighbours.
In the first decades of its existence, Tupelo developed as a classic trading hub of the agrarian South. The local economy relied on two main areas: cotton cultivation and large-scale logging, and established transport links allowed farmers to efficiently export their produce. Despite its initially modest size, the city quickly secured its status as a regional centre, attracting merchants and artisans, which laid a solid foundation for its future growth.