The Ponce de Leon was a named train of the Southern Railway which ran from Cincinnati, Ohio, to Jacksonville, Florida, from 1924 to the mid-1960s.

The Ponce de Leon (Train #4) departed Jacksonville at midday going north via subsidiary Georgia Southern and Florida Railroad to Macon and Atlanta, Georgia, then on Southern's former East Tennessee, Virginia and Georgia Railroad line to Chattanooga, Tennessee, traveling overnight to Cincinnati via Southern subsidiary Cincinnati, New Orleans and Texas Pacific Railway.

The train provided connections with the New York Central Railroad at Cincinnati for passengers headed to Detroit, Chicago, Cleveland, and Buffalo.

[3] By the time Southern Railway filed to discontinue the train on January 22, 1968 it was unnamed, operating as Numbers 1 and 2, but only between Cincinnati and Atlanta.

[5] The Ponce de Leon and Royal Palm collided on December 23, 1926 in Rockmart, Georgia.