The arrival of the railroad led to Amarillo's establishment, and the city is still a major rail crossroad. Two mainlines of the Burlington Northern Santa Fe Railway intersect at Amarillo, and provide direct service to Chicago, Los Angeles, Denver, Phoenix, Kansas City, Dallas, Seattle, Vancouver, Memphis, St. Louis and Pensacola. The mainlines also terminate at the ports of Houston, San Diego and Galveston.

The rail line operates a large intermodal facility in Amarillo that handles about 30,000 containers and trailers each year.The Union Pacific-Southern Pacific railroad also has rights to use BNSF tracks in the Amarillo area.