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The South Florida Railroad, built from Sanford to Tampa, Florida, was the first railroad to reach Sanford, Florida. It started operations on November 11, 1880, running between Sanford and Orlando.

In 1893, the Plant System took over the South Florida Railroad. In 1902, the Atlantic Coast Line Railroad took over the Plant System. Today, the former South Florida Railroad is part of the Central Florida Rail Corridor.

In the 1870s, the Jacksonville, Tampa & Key West Railway built a link between Sanford and Jacksonville, Florida. The railroad went bankrupt in 1893 and was operated by a receiver until 1899, when the receiver leased it to the Plant Investment Company. It was then operated as the Lake Eustis Division of the Plant System. It was sold to the Plant System in 1900 and fully merged into Plant’s Savannah, Florida & Western Railroad.

The Sanford and Lake Eustis Railway built westward from Sanford to Tavares, Florida, on Lake Eustis.

In 1885, Russian exile Peter Demens established the Orange Belt Railway, a narrow gauge line between Sanford and St. Petersburg, Florida. Later known as the Sanford & St. Petersburg Railroad, after an 1893 reorganization, the line carried citrus, vegetables, and passengers. In 1895, Henry B. Plant purchased the line, converted it to standard gauge and merged it into the Plant System.

Today, Sanford is the southern terminus of Amtrak’s Auto Train, which runs between Lorton, Virginia. Additionally, SunRail operates a station in Sanford.

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