The Sante Fe Railway was chartered by the Kansas territorial legislature in February 1859, under a charter written by Cyrus K. Holliday. Due to drought the following year and then the start of the Civil War, as well as difficulties finding a construction company, construction did not begin on the railroad until 1868.

In 1863, after President Lincoln signed a land grant bill providing the company with land on each side of its main roads and branches, the stockholders elected to change the name of the company to the Atchison, Topeka & Santa Fe Railway Company (ATSF).

From 1868 to 1873, construction of the rail line moved west across the state of Kansas to Colorado. By 1880 the railroad was operating in New Mexico. The main line never went to Santa Fe, due to difficult terrain; instead that city was served by a branch line.

Offices for the company started in Boston, Massachusetts and moved over the years to New York City and Topeka, the financial office remaining in Boston. In 1895 after the company restructured due to inability to pay its debts, all administrative functions of the company were consolidated in Chicago.

The ATSF offered passenger and freight service until 1971, when passenger service was taken over by Amtrak. ATSF was known for its luxurious passenger service, particularly after Fred Harvey established a chain of restaurants, hotels, and related businesses in association with the railroad.

In the mid-1990s the ATSF merged with Burlington Northern to form the Burlington Northern Santa Fe (BNSF) Railway.