The Santa Fe, completed in 1887, was the only railway into Oklahoma Territory and the only direct connection with the "outside" world during the hectic days of 1889. The first depot was a small red frame building located on the west side of the tracks. For the world's first big land run, the Santa Fe had only a single track leading through the new country. Guthrie was a watering station with rudimentary yards. Twenty trains carrying 1200 to 1500 passengers each were scheduled out of Arkansas City and Purcell on April 22, 1889; Guthrie was target destination for most of these.
The present two-story red brick station was completed in 1903 and housed passenger service, mail service, "Harvey House" restaurant, news stand, employee living quarters and offices.