The Rochester and Syracuse Railroad was incorporated on August 1, 1850. The Auburn and Rochester Railroad Company was incorporated May 13, 1836, and opened in August 1841. The Auburn and Syracuse Railroad Company was incorporated May 1, 1834, and opened in June 1838. Both railroads combined on August 1, 1850, and the consolidated company constructed the Direct Railway between Syracuse and Rochester.

The line has no name in the 1870 collection of railroads but does correspond with the Auburn Road on the Canandaigua, NY, 1:62,500 quad, 1900, USGS;  Macedon, NY, 1:62,500 quad, 1900, USGS;  Rochester, NY, 1:62,500 quad, 1895, USGS maps.  It is associated with Mark Twain's American Vandals Tour.

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