Although the community had existed for several years as Lenna City during the period of time in which the local railroad was built, Seffner was officially named after its first postmaster in 1884. Like many small Florida towns, it owes its existence and prosperity to H.B Plant and his railroad.

According to a local county historian, Seffner became a prosperous town with successful businesses including groves, a hotel, a drug store, several dry goods stores, and a livery stable. The town experienced a large population increase when the yellow fever epidemic hit Tampa in the fall of 1887 and in 1888, which caused many residents to flee Tampa in search of temporary domiciles. The beauty and popularity of the area was a driving force for others to relocate there. By 1925, Seffner was the fourth largest town in Hillsborough County. Today, Seffner boasts a population over 35,000.