The Kansas City Southern Railway Company was conceived by entrepreneur Arthur Edward Stilwell as a way to link the Midwest to international trading via the ocean. A rail line from Kansas City to the Gulf of Mexico would cover only 800 miles, whereas rail lines to ports on the Atlantic coast covered 1400 miles. Stilwell saw a line between Kansas City and the Gulf of Mexico as an opportunity to save on shipping costs. Stilwell and Kansas Citian, Edward Martin, began by creating the Kansas City Suburban Belt Railway which travelled from the Argentine District in Kansas City, Kansas, through the industrial districts of Kansas City and east to Independence, Missouri. This section of the Belt line was incorporated in 1887 and began operation in August 1890.

Stilwell's ideas continued to expand, extending a rail line further south to the Arkansas Oklahoma coal lands to become the Kansas City, Nevada and Fort Smith Railroad in 1889. This line also progressed through coal fields to the lead and zinc mines of Joplin, Missouri by 1893. By 1897, the Kansas City, Pittsburg and Gulf Railroad ran from Kansas City to the Gulf port city of Port Arthur, Texas. This length of railroad became The Kansas City Southern Railway (KCSR) Company in March 1900.

The acquisition of the Louisiana and Arkansas Railway Company in 1939 connected Kansas City to New Orleans. The Southern Belle offered luxury passenger service between the two cities from 1940 to 1969. In 1949, the Southern Belle housed 4 bedroom/4 roomette Pullman sleeping cars, diner and tavern-lounge-observation car, chair cars, and the latest improvements in mechanics. Shrinking revenue forced this service to close in 1969 and put full focus on freight service and continually improving technology.

In 1994, the KCSR acquired the MidSouth Rail Corporation. This brought the company into Mississippi, Tennessee, and Alabama. The corporation still sought expansion of the rail lines, and in 1995 entered into an agreement with the Mexican-based company Grupo TMM, S.A. de C.V. and purchased stock in the Texas Mexican Railway Company. This expanded the railway's reach into Mexico. The KCSR reached Panama with an investment in the Panama Canal Railway Company in 1998. In 2001, a merger took place with the Gateway Western Railway Company that moved the KCSR east toward Illinois. In 2012, the biggest business for the Kansas City Southern was their freight service that connected the Mid-West to Mexico and Panama; and with their oversea shipping relationships, throughout the world.