The station was along the Atchison, Topeka and Santa Fe Railway's main line and served trains such as the Super Chief and El Captain.

After Amtrak took over intercity rail in the United States, it was served by trains such as the Lone Star (1971–1979) and the Southwest Chief (1971–1996).

The Santa Fe Railway was originally planned to bypass Galesburg 10 to 12 miles to the southeast.

[18] The railway asked the city of Galesburg to remove the grade crossing with Cedar Street, directly west of the depot.

[20] To allow trains to switch freely between lines, a connector outside Cameron, Illinois (southwest of Galesburg) was built.