The northwest region of Alachua County was probably first settled on a permanent basis by English speaking people during the late 1830's. One of the earliest settlements `in the vicinity was at Crockett Springs, located about three miles east of present day High Springs. Settlers who were living there during the 1840's included Fernando Underwood and Marshal Blanton. No town developed in the area before the latter part of the nineteenth century. In 1884, the Savannah, Florida, and Western Railroad was extended from Live Oak to Gainesville. A post office and station were established here in that year under the name of Santaffey, which was a common spelling of the name of the nearby Santa Fe River. The town was also known unofficially as Orion before the name was changed in 1888 to High Springs. In the next few years, High Springs boomed as a result of the development of phosphate mining in the area. In 1892, the town was incorporated. During the next year, the Savannah, Florida, and Western Railroad completed its South Florida Division which connected High Springs with Port Tampa. By the beginning of the twentieth century, High Springs was known as an important railroad center. In later years, High Springs has been the focus for the surrounding agricultural region.
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