It was chartered by the state of Illinois in 1867 through the efforts of former American Civil War General Green B. Raum, who subsequently oversaw the planning and engineering of the proposed line.
The Cairo & Vincennes began laying track in 1870 and completed the initial portion in 1872 to haul coal from southern Illinois mines.
In January 1874, the railroad was teetering on bankruptcy and the contractors, the firm of Winslow & Wilson, applied for control.
In February, a new board of directors assumed control of the railroad and named industrialist J. P. Morgan as the new president, replacing Burnside.
With the exception of a small portion in Carmi, the entire line has been abandoned, though the right of way, with numerous concrete bridges, remains mostly intact.